Cyclo-PROGINOVA

Active material: Estradiol valerate, Norgestrel
When ATH: G03FB01
CCF: Protivoklimakterichesky drug
When CSF: 15.11.04.01
Manufacturer: BAYER SCHERING PHARMA AG (Germany)

DOSAGE FORM, COMPOSITION AND PACKAGING cycle-proginova

Drop two species.

Drops white (11 PC. in blister).

Excipients: corn starch, lactose monohydrate, magnesium stearate, povidone 25 000, talc.

The composition of the shell: wax, calcium carbonate, macrogol 6000, povidone 700000, sucrose, talc.

Drops of light brown color (10 PC. in blister).

Excipients: corn starch, lactose monohydrate, magnesium stearate, povidone 25 000, talc.

The composition of the shell: wax, glycerol 85%, calcium carbonate, dye iron oxide yellow, iron oxide red dye, macrogol 6000, povidone 700000, sucrose, talc, Titanium dioxide.

21 PC. – blisters (1) – packs cardboard.

Farmakologicheskie properties cyclo-PROGINOVA

Farmakodinamika

Cyclo-Proginova soderzhit эstrogen – estradiol valerate, in which the human body is converted into natural 17b-estradiol. Also in the product Cyclo-Proginova includes a derivative of progesterone – norgestrel. Adding norgestrel for 10 days of each cycle prevents the development of endometrial hyperplasia and cancer.

Due to the composition and cyclic regimen Cyclo-Proginova (receiving only estrogen for 11 days, then – a combination of estrogen and progestogen for 10 days, and, finally, 7-day break) women's non-removed uterus when taken regularly medication set the menstrual cycle.

While taking cyclo-Proginova suppress ovulation does not occur, and almost constant production of hormones in the body. Cyclo-Proginova can be used by women of childbearing age to regulate the menstrual cycle, and perimenopausal women to treat irregular uterine bleeding.

Estradiol restores estrogen deficiency in the female body after menopause and provides effective treatment of the psycho-emotional and vegetative menopausal symptoms (such as "hot flashes", increased perspiration, sleep disturbance, increased nervous irritability, irritability, heartbeat, kardialgii, dizziness, headache, decreased libido, muscle and joint pain); involution of the skin and mucous membranes, especially mucous membranes of the genitourinary system (urinary incontinence, dryness and irritation of the vaginal mucosa, pain during intercourse).

Estradiol prevents bone loss, caused by estrogen deficiency. This is mainly due to the suppression of osteoclast function and shift the process of bone remodeling toward the formation of bone. It has been proved, that long-term use of hormone replacement therapy (AFE) to reduce the risk of peripheral bone fractures in women after menopause. If you cancel HRT rate of decline of bone mass comparable to the, characteristic of the period immediately after the menopause. Not shown, what, using HRT, You can achieve restoration of bone mass to premenopausal levels.

HRT also has a beneficial effect on the collagen content in the skin, as well as its density, and may also slow down the formation of wrinkles.

HRT leads to a decrease in total cholesterol, low density lipoprotein cholesterol (LDL) and to increase HDL cholesterol (HDL), as well as increase the level of triglycerides. Progestogen, contained in the Cyclo-proginova to some extent prevent the effects of oestradiol on lipid metabolism.

Observational studies suggest, that among postmenopausal women using HRT reduced the incidence of colon cancer. The mechanism of action is unclear to date.

Pharmacokinetics

After oral administration of estradiol valerate is rapidly and completely absorbed from the gastrointestinal tract (GI). After entering the body, he quickly metaboliziretsya to form 17b-estradiol and estrone, which subsequently undergo metabolic transformations standard. Following oral administration, the bioavailability of estradiol about 3%. Eating does not affect the bioavailability of estradiol. The maximum concentration in serum estradiol, of approximately 30 pg / ml, usually achieved through 4-9 hours after receiving dragee. Estradiol is excreted as metabolites, mainly in the urine as sulfate and glucuronide.

After oral administration, norgestrel rapidly and almost completely absorbed from the gastrointestinal tract. The maximum concentration in serum levonorgestrel, of approximately 7-8 pg / ml, usually achieved 1-1,5 hours after receiving dragee. Levonorgestrel binds to albumin and globulin, sex hormone binding (SHBG). About 1-1,5% the total concentration levonorgestrel in serum is not associated with the protein. With a half-life, of approximately 1 day, norgestrel metabolites excreted in the urine and bile.

Indications cycle-proginova

Zamestitelynaya gormonalynaya therapy (AFE) when menopausal disorders, involutional changes in the skin and urinary tract, depressive conditions in menopause, as well as the symptoms of estrogen deficiency due to natural menopause or hypogonadism, sterilization or primary ovarian dysfunction in women with a uterus unremoved. Postmenopauzalynogo osteoporosis prevention. Normalization of irregular menstrual cycles. Treatment of primary or secondary amenorrhea.

Contraindications cyclo-PROGINOVA

It is not recommended to start hormone replacement therapy (AFE), if any of the following conditions. If any of these occur during the of Status of HRT, you should immediately discontinue use of the drug.

Pregnancy and lactation Vaginal bleeding of unknown origin confirmed or presumptive diagnosis of breast cancer confirmed or presumptive diagnosis of precancerous disease or hormone-hormone-dependent cancers of the liver tumors in the present or in history (benign or malignant) Severe liver disease, acute arterial thrombosis or thromboembolism (such as myocardial infarction, stroke) Deep vein thrombosis in the acute stage, thromboembolism present or in history of severe hypertriglyceridemia hypersensitivity to the drug Cyclo-Proginova.

The use caution cycle-proginova

Cyclo-Proginova be used with caution in the following diseases: arterial hypertension, congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson and Rotor), cholestatic jaundice or cholestatic pruritus during pregnancy, endometriosis, hysteromyoma, diabetes (cm. "Cautions").

Pregnancy and lactation, and the use of cyclo-proginova

HRT is not appointed during pregnancy or breast-feeding.

Large-scale epidemiological studies of steroid hormones, used for contraception or hormone replacement therapy, We found no increased risk of birth defects in children, born to women, those who took hormones before pregnancy, and teratogenic effects of hormones in their casual reception in the early stages of pregnancy.

Small amounts of sex hormones may be released from the mother's milk.

Dosage and administration cycle-proginova

If the patient is still ongoing menstruation, treatment should be started on the 5th day of the menstrual cycle (1-day of menstruation corresponds to the 1st day of the menstrual cycle).

Patients with amenorrhea or very infrequent menstruation, and postmenopausal women, can start taking the drug at any time, provided, that exclude pregnancy (cm. section "Pregnancy and lactation").

Each package is designed for a 21-day reception.

Every day during the first 11 days take one white pills, and then for 10 days - one daily light brown dragee. After the 21-day dosing should be a 7-day break in taking the drug, during which bleeding occurs menstrualnopodobnoe, caused by the abolition of the drug (usually 2-3 day after the last dragee).

After the 7-day break in taking the drug start a new pack Cyclo-Proginova, first taking pills on the same day of the week, that the first and last package of pills.

Drops proglatyvayut, drinking a small amount of liquid.

Times of Day, when a woman takes the drug, irrelevant, However, when she began taking pills at any particular time, it must adhere to this time and more. If a woman has forgotten to take pills, she can take it to the next 12 - 24 hours. If the treatment is interrupted for a longer time, you may experience vaginal bleeding.

Pobochnoe action cyclo-PROGINOVA

Reproductive system and breast:

changes in the frequency and intensity of uterine bleeding, breakthrough bleeding, intermenstrual spotting (usually weakens during therapy), dysmenorrhoea, change in vaginal discharge, state, podobnoe premenstrual syndrome; soreness, voltage and / or breast enlargement

From the gastrointestinal tract:

dyspepsia, abdominal distention, nausea, vomiting, abdominal pain, recurrence of cholestatic jaundice

Skin and subcutaneous tissue:

skin rash, itching, chloasma, uzlovataya эritema

CNS:

headache, migraine, dizziness, anxiety or depressive symptoms, fatigue

Other: cardiopalmus, swelling, high blood pressure, venoznыy thrombosis and tromboэmbolyya, muscle cramps, weight change, changes in libido, visual impairment, intolerance to contact lenses, allergic reactions.

Peredozirovka cyclo-PROGINOVA

There was no risk of serious side effects when taking the drug accidentally Cyclo-Proginova in quantity, many times greater than the daily therapeutic dose. Symptoms, which may occur with overdose: nausea, vomiting, vaginal bleeding.

No specific antidote, symptomatic treatment.

The interaction cycle-proginova with other drugs

At the start of HRT need to halt the use of hormonal contraceptives. If necessary, the patient should be advised that hormonal contraceptives.

Long-term treatment with drugs, inducing liver enzymes (eg, some anticonvulsants and antimicrobials) may increase the clearance of sex hormones and reduce their clinical efficacy. This property of inducing liver enzymes was found in hydantoins, ʙarʙituratov, prymydona, carbamazepine and rifampicin, availability of this feature is also expected to have oxcarbazepine, topiramate, felbamata and griseofulvin. Maximal enzyme induction is generally not seen before, than 2-3 of the week, but then it can persist, at least, during 4 weeks after stopping treatment.

In rare cases with concurrent ingestion of certain antibiotics (eg, penicillin and tetracycline groups) there was a reduction in estradiol levels.

Substances, highly exposed conjugation (eg, paracetamol), may increase the bioavailability of estradiol as a result of competitive inhibition of the conjugation system during absorption.

Because of the effect of HRT on glucose tolerance in some cases may change the need for oral antidiabetics or insulin.

Interaction with alcohol

Excessive consumption of alcohol during HRT may lead to an increase in circulating levels of estradiol.

Special instructions for the cycle-proginova

Cyclo-Proginova not applicable for contraception.

If necessary, contraception, should use non-hormonal methods (except for calendar and temperature methods). If you suspect a pregnancy, should stop taking the pills until, Pregnancy is not to be ruled out (cm. section "Pregnancy and lactation").

In the presence or worsening of any of the following conditions or risk factors, before you begin or continue HRT should weigh the individual risks and benefits of treatment.

Venous thromboembolism

A number of randomized controlled, tkazhe and epidemiological studies found an increased relative risk of developing venous thromboembolism (VTЭ) HRT, ie. deep vein thrombosis or pulmonary embolism. Therefore, the appointment of HRT to women with risk factors for VTE risk-benefit ratio of treatment should be carefully weighed and discussed with the patient.

Risk factors for VTE include a personal and family history (the presence of VTE in the immediate family at a relatively young age may indicate genetic predisposition) and severe obesity. The risk of VTE also increases with age. The question of the possible role of varicose veins in VTE remains controversial.

The risk of VTE may be temporarily increased during prolonged immobilization, "Large" and planned operations or massive trauma injury. Depending on the cause or duration of immobilization should decide whether a temporary cessation of HRT.

It should immediately stop treatment if symptoms of thrombotic disorders or suspected their appearance.

Arterial thromboembolism

In the randomized controlled trials of long-term use of combined conjugated estrogens and medroxyprogesterone acetate there was no evidence of a positive effect on the cardiovascular system. In large-scale clinical trials of this compound was found possible increased risk of coronary heart disease in the first year of application. There was also found an increased risk of stroke. So far, with other drugs for long-term hormone replacement therapy was conducted randomized controlled trials to identify a positive effect on morbidity and mortality, relating to the cardiovascular system. Therefore, it is not known, Does this increased risk of drugs for HRT, containing other types of estrogens and progestogens.

Endometrial cancer

With long-term unopposed estrogen increases the risk of endometrial hyperplasia or carcinoma. Studies have confirmed, that the addition of progestogen reduces the risk of endometrial hyperplasia and cancer.

Mammary cancer

According to the results of clinical trials and observational studies have found an increase in the relative risk of developing breast cancer in women, using HRT for several years. This may be due to earlier diagnosis, biological effects of HRT, or a combination of both factors. The relative risk increases with duration of treatment and possible further increases in combination with estrogen progestogen. This increase is comparable to the increased risk of breast cancer in women with every year of delay of natural menopause, as well as obesity and alcohol zloupotrebelnii. The increased risk gradually decreases to normal levels during the first few years after stopping HRT.

According to studies of breast cancer, identified women, taking HRT, usually more differentiated, than women not taking it.

HRT increases breast density breast, In some cases, it may adversely affect the radiological detection of breast cancer.

Liver tumors

Against the background of sex steroids, which include means for HRT, in rare cases benign, and even more rarely - malignant liver tumors. In some cases, these tumors have led to life-threatening intra-abdominal haemorrhage. When the pain in the upper abdomen, liver enlargement or signs of intra-abdominal haemorrhage in the differential diagnosis should take into account the likelihood of having a liver tumor.

Cholelithiasis

Known, Estrogens increase bile lithogenicity. Some women are predisposed to the development of gallstone disease during treatment with estrogen.

Other conditions

It should immediately discontinue treatment, when a migraine for the first time or frequent and unusually severe headaches, as well as other symptoms - possible precursors of thrombotic stroke brain.

The relationship between HRT and the development of clinically significant hypertension has not been established. Women, taking HRT, described a slight increase in blood pressure, clinically significant increase is rare. But, in some cases, in the development against the backdrop of HRT persistent clinically significant hypertension can be considered the abolition of HRT.

For non-severe hepatic dysfunction, including various forms of hyperbilirubinemia, such as Rubin-Johnson syndrome or Rotor syndrome, needed medical supervision, as well as periodic liver function tests. If deterioration in liver function HRT should be abolished.

At relapse cholestatic jaundice or cholestatic pruritus, observed for the first time during pregnancy or previous treatment of sex steroid hormones, you must immediately stop HRT.

The need for special monitoring of women with moderately elevated levels of triglycerides. In such cases, the use of HRT may cause a further increase in the level of triglycerides in the blood, thereby increasing the risk of acute pancreatitis.

Although HT can influence on peripheral insulin resistance and glucose tolerance, need to change the treatment regimen of patients with diabetes during HRT, usually does not occur. Nonetheless, women, diabetics, during HRT should be monitored.

Some patients under the influence of HRT may develop undesirable manifestations of estrogen stimulation, such as abnormal uterine bleeding. Frequent or persistent abnormal uterine bleeding during treatment is an indication for the study of the endometrium.

If the treatment of irregular menstrual cycles fails, should undertake a survey to exclude organic disease of character.

Under the influence of estrogen uterine fibroids may increase in size. In this case, treatment should be discontinued.

It is recommended to discontinue treatment with the development of recurrent endometriosis HRT.

If you suspect the presence of prolactinoma before treatment to exclude this disease.

In some cases, it may be observed chloasma, especially in women with a history of chloasma pregnant. During HRT women with a tendency to chloasma should avoid the emergence of long-term exposure to the sun or ultraviolet radiation.

The following conditions may occur, or may be aggravated by HRT. Although their relationship with HRT has not been proven, Women with these conditions during HRT should be under a doctor's supervision: epilepsy; a benign tumor of the breast; bronchial asthma; migraine; porphyria; otosclerosis; systemic lupus erythematosus, chorea.

Medical examinations and counseling in the application cycle-proginova

Before the beginning of the resumption of HRT or she will need to undergo a thorough general medical and gynecological examination (including the study of mammary glands and cytological examination of cervical mucus), exclude pregnancy. Besides, to exclude violations of blood coagulation. Periodically carry out test survey.

Effect on results of laboratory tests

Acceptance of sex steroids may influence biochemical parameters of liver function, Thyroid, adrenal glands and kidneys, on plasma levels of transport proteins, such as kortikosteroidsvyazyvayuschy globulin and lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis.

Effects on ability to drive and use mechanisms

It does not affect.

Product form

By 10 dragees light brown and 11 dragees white color is placed in a blister made of PVC film and aluminum foil. Each blister with self-adhesive calendar and receive instruction on use is placed in a cardboard box.

Storage conditions

Keep in places, inaccessible to children!

Shelf life

5 years.
Do not use beyond the expiration date, on the package!

Conditions of supply of pharmacies

On prescription. List B.