Pharmacological properties

Pharmacodynamics. progesterone — hormone of a yellow body of an ovary. promotes formation of normal secretory endometrium at women. causes transition of a mucous membrane of a uterus from a proliferation phase in a secretory phase, and after fertilization promotes its transition to a state necessary for oospore development. reduces excitability and contractility of muscles of a uterus and uterine tubes, stimulates development of final elements of a mammary gland. shows anti-androgenic activity, promotes increase in a diuresis due to antialdosteronovy action.

Progesterone is the hormone necessary for preservation of pregnancy throughout all its term: it slows down immunological reaction of a uterus to fruit antigens, is substrate for formation of glucocorticoids and mineralokortikoid of a fruit. Progesterone slows down spontaneous sokratitelny activity of a pregnant uterus and also is necessary for start of the mechanisms initiating childbirth.

Most important effects of influence of progesterone on reproductive organs are: a possibility of an ovulation by strengthening of proteolysis of a wall of a graafovy bubble; secretory change of endometrium that does possible oospore implantation; braking of an excessive hypertrophy of endometrium under the influence of effect of estrogen; cyclic changes in an epithelium of uterine tubes, neck of the uterus and vagina.

Other metabolic effects of effect of progesterone are fervescence, breath stimulation, decrease in concentration of amino acids in blood plasma, normalization of concentration of glucose in blood plasma, anti-androgenic action which consists in blocking of activity 5 - alpha reductases.

Pharmacokinetics. After introduction to a vagina, progesterone is quickly soaked up in a mucous membrane. After vaginal introduction of 100 mg of progesterone With _max in blood serum it is reached in 6–7 h and makes 10.1±4.7 mkg/ml. AUC for the progesterone entered vaginalno (100 mg), makes 86.6±40.7 ng · h/ml ^-1 .

Concentration of progesterone in blood serum are in limits of 5-15 mkg/ml that corresponds to a physiological early lyuteinovy phase and enough for implementation of secretory exchange of endometrium and preservation of pregnancy.

After vaginal introduction directly to uterus endometrium which is the physiological place of accumulation of hormone. Transportation of progesterone from a vagina in a uterus can be carried out on the mechanism of direct diffusion in fabric of endometrium, transportation through a neck, transportation with a venous and lymphatic blood-groove or way of the facilitated counterflow diffusion from absorbent and venous vessels to the arterial system of a uterus.

Concentration of progesterone in endometrium fabrics, expressed in ng/mg a squirrel, is higher after vaginal introduction, than after in oil. From endometrium progesterone is gradually released in the blood circulatory system depending on requirements of an organism.

Progesterone entered vaginalno gets into the blood circulatory system, passing metabolism in a liver. The t _½ progesterone entered intravaginalno makes about 13 h of blood serum. To be removed medicine with urine, generally in the form of metabolites which appear at physiological secretion of a body.

Indication

Vaginal tablets on 50 mg. treatment of the violations connected with deficiency of progesterone. violation of a menstrual cycle, painful periods, anovulatory cycles, a premenstrual syndrome, dysfunctional uterine bleedings, uterus endometriosis, the infertility connected with lyuteinovy insufficiency, a usual abortion and threat of an abortion against the background of deficiency of progesterone, insufficiency of a lyuteinovy phase of the premenopausal period and also in replacement hormonal therapy (zgt) and in programs of artificial fertilization.

Vaginal tablets on 100 mg. Treatment of endogenous deficiency of progesterone in the form of violations of a menstrual cycle, secondary amenorrhea, anovulatory cycles, a premenstrual syndrome, functional uterine bleedings. At artificial fertilization, the infertility connected with lyuteinovy insufficiency, a usual miscarriage and threat of a misbirth at deficiency of progesterone, insufficiency of a yellow body, a secondary amenorrhea, for prevention of a hypertrophy of endometrium at the women accepting estrogen (for example at ZGT), for treatment of endometriosis, in programs of in vitro fertilization (ECO), at ZGT at women after a menopause with an unextracted uterus for the purpose of protection of endometrium, for treatment of insufficiency of a lyuteinovy phase during the period before a menopause.

Vaginal tablets on 200 mg. It is recommended in the ECO programs.

lutein Dose in each separate case has to be established by

individually depending on indications and therapeutic effect. for more convenient application by patients and regulations of dosing exist such dosages of a lyuteina, vaginal tablets — 50 mg, 100 mg, 200 mg. vaginal tablets should be entered into a vagina by means of the applicator which invests in packing.

At violations of a menstrual cycle and a peredmenstrualny syndrome, insufficiency of a lyuteinovy phase during the period before a menopause to apply vaginalno 25–50 mg of progesterone 2 times a day in the 2nd phase of a menstrual cycle (natural or reproduced) within 10–12 days. To apply in the corresponding dosage.

At violations of a menstrual cycle, painful periods, a premenstrual syndrome the treatment by progesterone lasts 3–6 cycles in a row. At insufficiency of a lyuteinovy phase before a treatment menopause progesterone it is necessary to see to emergence of a menopause.

V ZGT in combination with estrogen are applied by 25–50 mg of progesterone vaginalno 2 times a day in consecutive therapy from the 15th to 25th day of a cycle or in continuous therapy daily. To apply in the corresponding dosage.

When performing progesteronovy test at a secondary amenorrhea progesterone are applied vaginalno in a dose of 50 mg by 2 times a day within 5–7 days. The periods have to appear within 7–10 days after the end of intake of progesterone. To apply in the corresponding dosage.

In treatment of functional uterine bleedings are applied on 50 mg of progesterone vaginalno by 2 times a day within 5–7 days. It is necessary to continue treatment 2–3 months in a row, applying progesterone in a dose of 25-50 mg 2 times a day vaginalno from the 15th to 25th day of a cycle. To apply in the corresponding dosage.

In endometriosis 50–100 mg of progesterone vaginalno 2 times a day in continuous therapy within 6 months

apply

At a usual miscarriage and threat of an abortion, the anovulatory and induced cycles 2 times a day apply vaginalno 50–150 mg of progesterone. In case of a usual miscarriage the use of progesterone should be begun in a cycle for which conception is planned. Treatment needs to be continued continuously till 18-20th week of pregnancy.

In the ECO programs are applied on 150–200 mg of progesterone by 2 times a day vaginalno. Treatment continue till 77th day after a transfer (movement) of a germ. The end of therapy has to happen by a gradual dose decline of medicine.

Contraindication

Hypersensitivity to medicine components. feeding period breast. the suspected or confirmed neoplasia of a breast or genitals. uncertain bleedings from a genital tract. heavy abnormal liver functions. cholestatic jaundice. a syndrome of the rotor and a syndrome of a dabin — Johnson. thromboembolic diseases of veins (thrombophlebitis of deep veins, pulmonary embolism). the available or postponed thromboembolic violations in arteries (stenocardia, a myocardial infarction). unsuccessful abortions and also existence of the remains after an abortion in a cavity of the uterus. porphyria, cerebral hemorrhage.

Side effects

At application of a lyuteina, the vaginal tablets containing the progesterone identical to endogenous hormone, side effects arose sporadically.

In some cases noted drowsiness, violation of concentration and attention, sensation of fear, depressions, a headache and dizziness, insomnia.

from a reproductive system: abnormal bleedings from a uterus, a dysmenorrhea, bloody discharges, an amenorrhea, premenstrual symptoms, the alternating bleedings, a mastodynia, changes of a libido, discomfort in a breast.

from skin and its appendages: erubescence, eels, allergic reactions, urticaria, itch, alopecia, hirsutism, anaphylactic reactions, hloazma.

from digestive system: nausea, dryness in a mouth, an odontorrhagia, cholestatic jaundice, gastrointestinal frustration, vomiting, diarrhea, a lock.

from the vascular system: thrombosis, venous thrombembolia, embolism of a pulmonary artery.

Other violations: liquid delay, hyperthermia.

Special instructions

Progesterone entered intravaginalno gets directly into the blood circulatory system, without participating in hepatic metabolism. in this regard patients have no need for dose adjustment of medicine with an abnormal liver function.

Prior to treatment should perform gynecologic examination and a palpation of mammary glands. If the course of treatment begins very much early at the beginning of a monthly cycle, especially till 15th day of a cycle, can reveal reduction of a cycle or bleeding. In case of uterine bleedings it is not necessary to appoint medicine without establishment of their reason. At emergence of an amenorrhea it is necessary to be convinced of lack of pregnancy.

Patient with a depression have to be in the anamnesis under special observation as progesterone can cause strengthening of a depression.

effect of contraception. In case of use of progesterone for other reasons which are not connected with infertility it is necessary to apply contraceptive means at the same time. It is necessary to warn patients about obligatory informing the doctor at identification of changes in a mammary gland.

Use of medicine for patients of premenopausal age can hide the beginning of a menopause.

should not use medicament to patients with heavy abnormal liver functions.

Patient with diseases of a liver have to be under observation of the doctor during treatment.

after the postponed thromboembolic violations: the available or postponed arterial or venous thromboembolic violations, including thrombophlebitis of deep veins, a pulmonary embolism, stenocardia, a myocardial infarction.

With care with a liquid delay (for example owing to AG, a disease of a cardiovascular system, kidneys and also the patient with epilepsy, migraine, OH), diabetes, photosensitivity.

Before prescribing of medicine should examine carefully patients with existence of new growths in the family anamnesis and with a recurrent cholestasia or constant feeling of an itch during pregnancy, an abnormal liver function, a heart or renal failure, fibrotsistny mastopathy, epilepsy, OH, an otosclerosis, diabetes, multiple sclerosis, a system lupus erythematosus.

Before an initiation of treatment the patient has to undergo careful medical and careful gynecologic examination, including intra vaginal and mammology inspection, Papanikolau's smear, taking into account the given anamnesises, contraindications and precautionary measures at application. During treatment it is recommended to have regular examinations at the doctor.

to Women who receive ZGT should estimate carefully the ratio risk/advantage connected with therapy.

At patients with post-menopausal symptoms which receive or were received by ZGT, there is a weak or moderate increase in probability of diagnosing of a breast cancer. It can be connected with early identification of patients or the actual advantage of ZGT and also their combination. The risk of developing of a breast cancer increases with increase in duration of treatment and is restored to initial values in 5 years after the termination of reception of ZGT. The breast cancer which is diagnosed for the patients who are receiving or recently receiving ZGT is less invasive, than what arises at the women who did not undergo treatment of ZGT. The doctor has to discuss higher probability of development of a breast cancer with patients who will receive long-term hormonal therapy, estimating advantages of ZGT.

Drug contains lactose therefore it should not be applied at patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption.

Use of medicine for patients of premenopausal age can hide the beginning of a menopause.

Drug contains lactose therefore it should not be applied at patients with the most rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption.

Due to the thromboembolic and metabolic risk which cannot be excluded completely needs to stop administration of medicament in case of approach:

• visual violations, such as loss of sight, doubling in eyes, vascular damages of a retina;
• tromboembolic venous or trombotichesky episodes, irrespective of the site of defeat;
• a severe headache.

in case of the tromboflebitichesky anamnesis the patient has to be under strict observation.

More than a half of early involuntary abortions are caused by genetic complications. Besides infectious manifestations and mechanical violations can be the cause of early abortions; the delay of exile of dead egg would be uniform reasonable prescribing of progesterone then. Thus, prescribing of progesterone according to the recommendation of the doctor has to be provided for cases when progesterone secretion insufficient.

Use during pregnancy and feeding by a breast. Progesterone can be applied in the I trimester of pregnancy. Does not render the masculinizing, virilizing, kortikoidny and anabolic action. Clinical information on use of progesterone in II and III trimester of pregnancy is not enough. Use of progesterone during feeding by a breast contraindicated in view of penetration of hormone into breast milk.

hypospadias given about possible risk of development at use of progestogens during pregnancy for prevention of a usual abortion or threat of an abortion against the background of lyuteinovy insufficiency what it is necessary to inform the patient on Exists.

Children. There are no data.

Influence on ability to steer vehicles and to work with difficult mechanisms. Due to the possible emergence of drowsiness and violation of concentration of attention it is necessary to refrain from control of vehicles and work with other mechanisms. At use of progesterone the dizziness, drowsiness, violation of concentration and attention are in rare instances possible what it is necessary to warn the patient about. Use of tablets before going to bed allows to avoid these unpleasant consequences.

Interaction

Clinically significant interactions with other medicines was not noted. in the researches in vitro it is revealed that the medicines reducing activity of cytochrome r450 (for example ketokonazol), can slow down progesterone metabolism. the clinical value of this influence is unknown.

to increase in removal from an organism of sodium and chlorides.

Progestins reduce tolerance to glucose that can lead to increase in a daily dose of insulin or other anti-diabetic medicines at patients with diabetes.

Use of progesterone can increase concentration of cyclosporine in blood plasma. Some antibiotics (for example ampicillin, tetracycline) can cause changes of intestinal microflora, change of a hepatic steroid cycle is a consequence of what.

Powerful inductors of liver enzymes, namely: barbiturates, antiepileptic medicines (Phenytoinum), rifampicin, phenylbutazone, Spironolactonum, griseofulvin, not Virapinum, efavirents, carbamazepine — increase metabolism at the hepatic level. Ritonavir and nelfinavir are known as powerful inhibitors of enzymes of cytochrome, show enzyme - the inducing properties at simultaneous application with nonsteroid hormones.

Overdose

Symptoms of side effect, as a rule, arise owing to overdose.

Most frequent symptoms are drowsiness, dizziness, a depression.

Symptoms, as a rule, disappear independently after a medicine dose decline.

For some patients high in connection with hypersensitivity to medicament or the low accompanying oestradiol level in blood or existing or secondary emergence of unstable endogenous secretion of progesterone.

In such cases:

• to lower a dose of medicine or to apply it in the evening before going to bed for 10 days of a cycle in case of drowsiness or short-term dizziness;
• to transfer an initiation of treatment to later term in a cycle (for example for the 19th day instead of the 17th) in case of its reduction or emergence of a krovomazaniye;
• to check oestradiol level at the patient receiving ZGT during the premenopausal period.

Storage conditions

B the dry place protected from light at a temperature not above 25 °C.