Ovipol Klio®

General characteristics. Structure:

Active ingredient: 0,5 mg of estriol.

Excipients: semi-synthetic glycerides (like Suppotsir).

Pharmacological properties:

Pharmacodynamics. The estrogen synthesized in a human body. Getting to a blood stream, forms a complex with specific receptors (in a uterus, a vagina, an urethra, chest gland, a liver, a hypothalamus, a hypophysis), stimulates synthesis of DNA and proteins. Possesses the selection action, it is preferential on a neck of uterus, a vagina, a vulva, causes strengthening of proliferation of an epithelium of a vagina and neck of uterus, stimulates its blood supply, promotes recovery of an epithelium at its atrophic changes during the periods of a premenopauza and menopause, normalizes рН the vulval environment, vagina microflora, increases the resilience of its epithelium to infectious and inflammatory processes, exerts impact on quality and amount of cervical slime.

Impact on an endometria is insignificant (insignificant risk of uterine bleedings). Has hypolipidemic effect, slightly increases concentration in blood of beta lipoproteins, increases sensitivity to effect of insulin, improves glucose utilization, stimulates development with a liver of the globulins connecting sex hormones, a renin, LPVP and blood-coagulation factors. Thanks to participation in implementation of positive and negative feedback in гипоталамо - pituitary and ovarian system estriol is capable to cause moderately expressed central effects; stimulates parasimpatikomimetichesky reactions.

Pharmacokinetics. Absorption is high. Time of achievement of the maximum concentration in a blood plasma at intravaginalny use - 1-2 h. Linkng with albumine of plasma makes 90%.

Removal is carried out generally by kidneys in the form of metabolites (in several hours after reception and proceeds to 18 h), 2% are removed through intestines in not changed look

Indications to use:

Replacement hormonal therapy: the mucosal atrophy of lower parts of an urogenital path connected with deficit of estrogen.

Before - and postoperative therapy at women in a postmenopause to whom it is necessary or operation is performed by vulval access.

With the diagnostic purpose at not clear results of a smear from a vagina against the background of atrophic changes.

Route of administration and doses:

Intravaginalno, before going to bed. At a mucosal atrophy of lower parts of an urogenital path  appoint on 1 suppository (0,5 mg) daily in the first 2-3 weeks, then gradually reduce a dose, based on symptomatology, 1 suppository (0,5 mg) 2 times a week.

Before - and postoperative therapy at women in a postmenopause - on 1 suppository (0,5 mg) during 2 weeks to or after operation.

As diagnostic means - 1 suppository every other day within a week before capture of the following smear.

If the next dose of drug was passed, it is necessary to accept it immediately. However, if it was found only in day of reception of the following dose, it is necessary to continue administration of drug according to the usual scheme, without filling the passed dose. It is impossible to apply two doses in one day.

Features of use:

At prolonged treatment estrogen showed performing systematic medical examinations. Before reception and each 6 months of treatment it is necessary to conduct careful general medical and gynecologic examination, including inspection of mammary glands.

The Replacement Hormonal Therapy (RHT) at treatment of climacteric symptoms is recommended to be begun only if they adversely influence quality of life of the patient. In all other cases it is necessary to compare a ratio of advantage and risk. At younger age the ratio of advantage and risk is more favorable, than at women of advanced age. During treatment it is necessary to inform the doctor on cases of vaginal bleeding, on changes in mammary glands, emergence of jaundice, and also on emergence of symptoms of a thrombembolia (for example, painful hypostasis of extremities, a sudden stethalgia, an asthma). In all cases of the patient demand careful inspection.                                                                                                                         

Reasons for immediate cancellation of therapy:

- jaundice or abnormal liver function;
- increase in arterial pressure;
- developing of a headache as migraine;
- phlebitis.

Tumors. At long monotherapy by estrogen the risk of development of a hyperplasia or endometrial cancer which is directly proportional to a dose of drug and duration tera-Pius increases.

The risk of development of a breast cancer depends on ZGT duration, but in several years (most often 5 years) after the termination of therapy is returned to norm. Against the background of ZGT density of tissue of mammary gland can increase that complicates its radiological research.
Long therapy by estrogen (5-10 years) is also connected with increase in risk of development of ovarian cancer.

Against the background of use of sex hormones benign or malignant tumors of a liver were in rare instances observed. In some cases these tumors led to development of the intra belly bleeding posing a threat for life. At emergence of pains in an upper part of a stomach, increase in a liver or symptoms of intra belly bleeding at differential diagnosis it is necessary to consider existence of a tumor of a liver.

Cardiovascular diseases. ZGT is connected with increase in risk of development of venous thromboembolisms (VTE) by 1,3-3 times and is most probable within the first year of use of drug, than in later terms. It is necessary to consider all risk factors of VTE, and at purpose of drug before carrying out surgical intervention it is necessary to carry out prevention of VTE, and also it is necessary to cancel temporarily ZGT in 4-6 weeks prior to surgery and to resume treatment only after the woman starts walking.

The risk of an ischemic stroke especially increases at advanced age (see the section "Contraindications"). In the absence of VTE in the anamnesis, but in the presence of thrombosis at young age at the immediate family, it is recommended to conduct a screening on existence of trombofilichesky disturbances. At detection of the trombofilichesky defect not identical to a disease at relatives, or existence of "heavy" defect (for example, deficit of antithrombin, a protein of S or a protein With, or a combination of these defects), ZGT is contraindicated (see the section "Contraindications").

Women who receive treatment by anticoagulants need to compare a ratio of advantage and risk. Estrogen can cause a liquid delay. Patients with renal or heart failure during reception of ZGT have to be under observation of the doctor.            

Other states. Estrogen increases a bile litogennost that increases predisposition at some patients to development of cholelithiasis at use of estrogen. Estrogen is a weak antagonist of a gonadotrophin and does not exert significant impacts on endocrine system.

Cognitive function against the background of ZGT does not improve. Data on the increased risk of development of dementia in the women who began to accept continuously combined ZGT or monotherapy by estrogen after 65 years are obtained.

In case of identification of a prolaktinoma, the patient has to be under careful medical observation (including periodic assessment of concentration of prolactin). At women with hereditary factors of a Quincke's disease exogenous estrogen can cause or worsen symptoms of a Quincke's disease.

Influence on ability to manage vehicles and mechanisms. Drug influence Ovipol of Klio® on ability to manage vehicles and mechanisms is not revealed.

Side effects:

Itch and irritation in an injection site, tension and morbidity of mammary glands.

In a combination from gestagena: benign and malignant estrogenzavisimy tumors, including a breast cancer and an endometria, a venous thromboembolism, including deep veins of a shin and a small pelvis, pulmonary veins, a myocardial infarction, a stroke, diseases of a gall bladder, a hloazm, a multiformny erythema, a knotty erythema, a hemorrhagic purpura, dementia at the beginning of ZGT in continuous administration of drug after 65 years, acyclic bloody allocations, bleedings of "break", increase in a libido.

Interaction with other medicines:

Inductors of a microsomal oxidation (phenobarbital, carbamazepine, Phenytoinum, rifampicin, рифабутин, not Virapinum, эфавиренз) strengthen metabolism of estrogen; powerful in-gibitor (ритонавир, нелфинавир) - considerably oppress metabolism.

Drugs of the St. John's Wort which is made a hole can induce metabolism of estrogen.

Estriol strengthens action of hypolipidemic means.

Weakens effects of male sex hormones, anticoagulants, antidepressants, diuretic, hypotensive, hypoglycemic means.

Contraindications:

Hypersensitivity, established (including in the anamnesis) or the suspected breast cancer, estrogenzavisimy malignant new growths or suspicion on them (including endometrial cancer), not diagnosed genital bleeding, not treated hyperplasia of an endometria, fibrinferment (venous and arterial) and thromboembolisms now or in the anamnesis (including, a deep vein thrombosis, a thromboembolism of a pulmonary artery, a myocardial infarction, a stroke), cerebrovascular disturbances; the states preceding thrombosis (including, the tranzitorny ischemic attacks, stenocardia) now or in the anamnesis; the multiple or expressed risk factors of venous or arterial thrombosis (including the complicated defeats of the valve device of heart, fibrillation of auricles, diseases of vessels of a brain or coronary arteries; uncontrollable arterial hypertension, serious surgical intervention with a long immobilization, smoking is aged more senior than 35 years); the confirmed thrombophilias, the hereditary or acquired factors contributing to development of venous and arterial thromboses such, as: resistance to the activated protein With, deficit of antithrombin III, deficit of a protein With, deficit of a protein of S, existence of antibodies to phospholipids and others; thrombophlebitis of deep veins, including in the anamnesis; the expressed gipertriglitseridemiya; cholestatic jaundice; an otosclerosis (including, in time before - the striding pregnancy or at treatment by sex hormones); acute diseases of a liver or existence of diseases of a liver in the anamnesis until indicators of hepatic function not to return to norm, a porphyria, pregnancy, the lactation period.

With care. A leiomyoma or endometriosis, a thrombembolia in the anamnesis or risk factors of its development, risk factors of estrogenzavisimy tumors, including the 1st degree of relationship on a breast cancer in the family anamnesis, arterial hypertension, liver diseases (including adenoma), a diabetes mellitus with a diabetic angiopatiya or without it, a cholelithiasis, migraine or a heavy headache, a system lupus erythematosus, epilepsy, bronchial asthma, a family giperlipoproteinemiya, pancreatitis, cancer or a hyperplasia of an endometria in the anamnesis, a heart or renal failure, metabolic disturbances of a bone tissue, herpes during the previous pregnancy.

Overdose:

At intravaginalny use the overdose is improbable. Symptoms (at accidental intake): nausea, vomiting, bleedings of "cancellation".

Treatment: symptomatic. There is no specific antidote.

Storage conditions:

In the dry, protected from light place, at a temperature from 15 to 25 °C. To store in the place, unavailable to children. A period of validity - 3 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Suppositories vaginal 0,5 mg. On 5 suppositories in a blister strip packaging. 3 blister strip packagings together with the application instruction in a pack from a cardboard.