Composition, form of production and packaging
? Suppositories vaginal white or white with a yellowish hue of color, cylindrical form; the presence of an air or funnel-shaped depression is allowed on the cut.
1 supp.
estriol 500 mcg
Excipients: semi-synthetic glycerides (of the "Suppocyr" type) - 1999.5 mg.
5 pieces. - packings cellular planimetric (3) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Estrogen, synthesized in the human body. Getting into the bloodstream, forms a complex with specific receptors (in the uterus, vagina, urethra, breast, liver, hypothalamus, pituitary), stimulates the synthesis of DNA and proteins. Has a selective effect, mainly on the cervix, vagina, vulva, increases the proliferation of the epithelium of the vagina and cervix, stimulates its blood supply, promotes the recovery of the epithelium during its atrophic changes during the periods of premenopause and menopause, normalizes the pH of the vaginal environment, the microflora of the vagina, increases its resistance epithelium to infectious and inflammatory processes, affects the quality and quantity of cervical mucus. The effect on the endometrium is insignificant (a slight risk of uterine bleeding).
Has hypolipidemic effect, slightly increases the concentration in the blood of beta-lipoproteins, increases sensitivity to the action of insulin, improves the utilization of glucose, stimulates the production of liver globulins, binding sex hormones, renin, HDL and clotting factors. Due to participation in the realization of positive and negative feedback in the hypothalamic-pituitary-ovarian system, estriol is able to cause moderately pronounced central effects; stimulates parasympatomimetic reactions.
PHARMACOKINETICS
Absorption is high. Time to reach C max in blood plasma for intravaginal application is 1-2 hours. Binding to plasma albumins is 90%.
Excretion is carried out mainly by kidneys in the form of metabolites (several hours after ingestion and lasts up to 18 hours), 2% is excreted through the intestine in unchanged form.
INDICATIONS
- hormone replacement therapy with atrophy of the mucosa of the lower sections of the urogenital tract associated with estrogen deficiency;
- pre- and postoperative therapy in postmenopausal women who are undergoing or have undergone vaginal surgery;
- with a diagnostic purpose for unclear results of a swab from the vagina on the background of atrophic changes.
DOSING MODE
Intravaginal, before bedtime.
At an atrophy of the mucous membrane of the lower sections of the urogenital tract , 1 supp is prescribed. (0.5 mg) daily in the first 2-3 weeks, then gradually reduce the dose, based on the symptomatology, 1 supp. (0.5 mg) twice a week.
Pre and postoperative therapy in postmenopausal women - 1 supp. (0.5 mg) for 2 weeks before or after surgery.
As a diagnostic tool - 1 soup. every other day for a week before taking the next smear.
If the next dose of the drug has been missed, you should take it immediately. However, if it was found only on the day of the next dose, you should continue taking the drug in the usual way, not filling the missed dose. Do not use 2 doses in one day.
SIDE EFFECT
Probably: itching and irritation at the injection site, tension and soreness of the mammary glands.
In combination with gestagens: benign and malignant estrogen-dependent tumors (including breast and endometrial cancer), venous thromboembolism (including deep veins of the lower leg and pelvis, pulmonary veins), myocardial infarction, stroke, gallbladder disease , chloasma, erythema multiforme, erythema nodosum, hemorrhagic purpura, dementia at the onset of HRT in the continuous administration of the drug after 65 years, acyclic bleeding, bleeding "breakthrough", increased libido.
CONTRAINDICATIONS
- established (including in anamnesis) or suspected breast cancer;
- estrogen-dependent malignant neoplasms or suspicion of them (including endometrial cancer);
- undiagnosed genital bleeding;
- untreated endometrial hyperplasia;
- Thrombosis (venous and arterial) and thromboembolism at present or in the anamnesis (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), cerebrovascular disorders;
- conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in the anamnesis;
- Multiple or expressed risk factors for venous or arterial thrombosis (including complicated heart valve disease, atrial fibrillation, cerebrovascular or coronary artery disease, uncontrolled arterial hypertension, serious surgical intervention with prolonged immobilization, smoking over the age of 35 years );
- confirmed thrombophilia, hereditary or acquired factors predisposing to the development of venous and arterial thromboses, such as: resistance to activated protein C, deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, the presence of antibodies to phospholipids and others;
- Thrombophlebitis of deep veins (including in the anamnesis);
- severe hypertriglyceridemia;
- cholestatic jaundice;
otosclerosis (including during the previous pregnancy or with the treatment of sex hormones);
- acute liver disease or presence of liver diseases in anamnesis until the parameters of the liver function return to normal;
- porphyria;
- Pregnancy;
- lactation period;
- Hypersensitivity to the components of the drug.
With caution: leiomyoma or endometriosis, history of thromboembolism or risk factors for its development, risk factors for estrogen-dependent tumors, incl. The first degree of kinship in breast cancer in a family history, hypertension, liver disease (including adenoma), diabetes mellitus with or without diabetic angiopathy, cholelithiasis, migraine or severe headache, SLE, epilepsy, bronchial asthma , familial hyperlipoproteinemia, pancreatitis, endometrial cancer or hyperplasia in the anamnesis, cardiac or renal insufficiency, metabolic bone disorders, herpes during the previous pregnancy.
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution apply the drug for kidney failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in acute liver disease or liver disease in history until the liver function is returned to normal.
APPLICATION IN ELDERLY PATIENTS
Data were obtained on the increased risk of dementia in women who started taking continuously combined HRT or monotherapy with estrogens after 65 years.
SPECIAL INSTRUCTIONS
With prolonged treatment with estrogens, systematic medical examinations are shown. Before starting the treatment and every 6 months of treatment, a thorough general medical and gynecological examination, including a breast examination, should be carried out.
Hormone replacement therapy (HRT) in the treatment of climacteric symptoms is recommended to start only if they adversely affect the quality of life of the patient.In all other cases it is necessary to compare the ratio of benefit and risk. At a younger age, the benefit-risk ratio is more favorable than that of older women. During treatment it is necessary to inform the doctor about cases of vaginal bleeding, changes in the mammary glands, the appearance of jaundice, as well as the appearance of signs of thromboembolism (eg, painful swelling of the extremities, sudden chest pain, shortness of breath). In all cases, the patient requires a thorough examination.
Reasons for immediate withdrawal of therapy:
- jaundice or liver dysfunction;
- Increased blood pressure;
- occurrence of a headache as migraine;
- phlebitis.
Tumors
With prolonged monotherapy with estrogen, the risk of developing hyperplasia or endometrial cancer is increased, which is directly proportional to the dose of the drug and the duration of therapy.
The risk of developing breast cancer depends on the duration of HRT, but a few years (more often than 5 years) after the cessation of therapy returns to normal.Against the background of HRT, the density of the breast tissue can increase, which complicates its radiological study.
Long-term estrogen therapy (5-10 years) is also associated with an increased risk of ovarian cancer.
On the background of the use of sex hormones in rare cases, benign or malignant liver tumors were observed. In some cases, these tumors led to the development of a life-threatening intra-abdominal bleeding. When there are pains in the upper abdomen, liver enlargement or signs of intra-abdominal bleeding, differential diagnosis should take into account the presence of a liver tumor.
Cardiovascular diseases
HRT is associated with an increase in the risk of venous thromboembolism (VTE) in 1.3-3 times and is most likely during the first year of use of the drug than at a later date. All risk factors for VTE should be considered, and when prescribing a drug before surgery, it is necessary to prevent VTE, and it is necessary to temporarily cancel HRT 4-6 weeks before surgery and resume treatment only after the woman starts walking.
The risk of ischemic stroke is especially increased in old age.
In the absence of VTE in the anamnesis, but in the presence of thrombosis at a young age with the next of kin, it is recommended to conduct a screening examination for the presence of thrombophilic disorders. If there is a thrombophilic defect that is not identical to that of relatives, or if there is a severe defect (eg, an antithrombin deficiency, protein S or protein C deficiency, or a combination of these defects), HRT is contraindicated.
Women who are treated with anticoagulants need to compare the benefit / risk ratio.
Estrogens can cause fluid retention. Patients with renal or heart failure during HRT should be monitored by a physician.
Other states
Estrogens increase the lithogenicity of bile, which increases the predisposition in some patients to the development of cholelithiasis with the use of estrogens.
Estrogens are a weak antagonist of the gonadotropin and have no significant effects on the endocrine system.
Cognitive function does not improve with HRT. Data were obtained on the increased risk of dementia in women who started taking continuously combined HRT or monotherapy with estrogens after 65 years.
In case of detection of prolactinoma, the patient should be under careful medical supervision (including periodic evaluation of prolactin concentration).
In women with hereditary factors of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.
Impact on the ability to drive vehicles and manage mechanisms
The effect of Ovipol Cleo В® on the ability to drive vehicles and mechanisms is not revealed.
OVERDOSE
In case of intravaginal administration, an overdose is unlikely.
Symptoms (with occasional ingestion): nausea, vomiting, bleeding "cancellation."
Treatment: symptomatic. There is no specific antidote.
DRUG INTERACTION
Microsomal oxidation inductors (phenobarbital, carbamazepine, phenytoin, rifampicin, rifabutin, nevirapine, efavirenz) increase the metabolism of estrogens;powerful inhibitors (ritonavir, nelfinavir) - significantly inhibit metabolism.
St John's wort preparations can induce estrogen metabolism.
Estriol enhances the action of lipid-lowering agents.
Weakens the effects of male sex hormones, anticoagulants, antidepressants, diuretic, hypotensive, hypoglycemic agents.
TERMS OF RELEASE FROM PHARMACY
The drug is approved for use as a means of OTC.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry, protected from light, out of reach of children, at a temperature of 15 В° to 25 В° C. Shelf life - 3 years.
