Composition, form of production and packaging
The tablets covered with a cover 1 tab.
Estradiol (in the form of hemihydrate) 1 mg
norethisterone acetate 500 mcg
28 pcs. - PVC blisters / Aluminum (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Revmelid is a combined preparation containing estrogen and progestogen, which is intended for continuous hormone replacement therapy.
Estradiol: the active ingredient, synthetic 17? -estradiol, by chemical structure and biological properties is identical to human endogenous estradiol. Eliminates the deficiency of estrogen in postmenopausal women and reduces the severity of the symptoms of menopause. Estrogens prevent the reduction of bone mineralization caused by menopause or ovariectomy.
Norethisterone: additional administration of progestogen significantly reduces the risk of hyperplasia, endometrium; caused by estrogen, in women who have not undergone hysterectomy.
PHARMACOKINETICS
After ingestion, estradiol is rapidly absorbed in the gastrointestinal tract. C max in plasma is achieved 6 hours after taking 2 mg. Metabolism of estradiol occurs mainly in the intestine and liver and includes the formation of less active metabolites (estrone, estriol, catechol estrogens, sulfates and glucuronides). Estradiol and metabolites are in plasma, mainly in protein-related conditions, mainly with sex hormone binding globulins (SHBGs), and to a lesser extent, with albumins. It is excreted as metabolites and unchanged in kidneys, a small amount through the intestine. T 1/2 is 12-14 hours. There is a significant interindividual variability, pharmacokinetic. indicators. Norethisterone acetate is rapidly absorbed after oral administration and is converted to norethisterone. C max in plasma is achieved 2 hours after taking 1 mg. Norethisterone binds to SHBG and albumin. It is subjected to presystemic metabolism in the liver and intestine.
Metabolites of norethisterone are excreted mainly by the kidneys in the form of sulfates and glucuronides. T 1/2 is about 8-11 hours.
INDICATIONS
- hormone replacement therapy (HRT) in women with symptoms of estrogen deficiency that are at least 1 year in postmenopausal women;
- prevention of osteoporosis in postmenopausal women in the case of high risk of bone fractures in those patients who do not tolerate or who are contraindicated in other drugs intended
for the prevention of osteoporosis.
DOSING MODE
Take inside, without chewing, 1 tablet 1 time per day without interruption, preferably at the same time every day.
If, after 3 months of treatment, the therapeutic effect is unsatisfactory, it may be necessary to switch to taking another combination drug with a higher content of hormones.
In the case of the prevention of climacteric osteoporosis, the effect of hormone replacement therapy on the mineral mass of bones is dose-dependent.
If you miss a regular tablet, the unaccepted pill should not be taken. The next pill is taken the next day.
SIDE EFFECT
The most common side effects observed in approximately 10-20% of patients in clinical studies with low doses of HRT are vaginal bleeding, tenderness, or pain in the mammary glands. Bleeding from the vagina, usually occurred in the first months of treatment. The pain in the mammary glands, usually, disappeared after several months of treatment.
Very frequent (> 1/10) Frequent (> 1/100, <1/10) Infrequent (1/1000, <1/100) Rare (> 1/10000, <1/1000)
Infections and invasions of vaginal candidiasis or vaginitis
Disorders from the immune system of the hypersensitivity reaction
Metabolic and nutritional disorders fluid retention, peripheral edema, weight gain
Mental disorders, depression, worsening of its course Irritability, possible dementia, insomnia, anxiety, changes in libido
Nervous system disorders headache, migraine or worsening migraine course dizziness, cerebral circulation disorder
Disorders from the cardiovascular system Thrombophlebitis of superficial veins Deep vein thromboembolism, thrombosis, pulmonary embolism, arterial hypertension
Disorders from the digestive system of abdominal pain, a feeling of discomfort in the abdomen, nausea flatulence, bloating
Disturbances from the skin and subcutaneous tissue alopecia, hirsutism, acne, skin itching, urticaria, skin rash
Disturbances from the musculoskeletal system and connective tissue cramps in the calf muscles, back pain arthralgia, myalgia
Disorders from the reproductive system and mammary gland pain or soreness of the mammary glands, bleeding from the vagina swelling of the breast or enlargement of its size, uterine fibrosis, worsening of the uterine fibrosis or relapse of its endometrial hyperplasia, dysmenorrhea breast cancer, vulvar-vaginal itching
Systemic disorders or reactions at the site of administration peripheral edema ineffective drug
Other chloasma, exudative polymorphic erythema, erythema nodosum vascular purpura impaired vision
Very rare side effects: weight loss; estrogen-dependent benign and malignant tumors, for example, endometrial cancer; myocardial infarction; cholecystitis, cholelithiasis; dementia.
CONTRAINDICATIONS
- Breast cancer (in the anamnesis, as well as suspicion of it);
- malignant estrogen-dependent tumors (eg, endometrial cancer) or suspected of them;
- bleeding from the vagina (including due to metrorrhagia of unknown origin);
- endometrial hyperplasia in the absence of treatment;
- factors of high risk of venous and arterial thrombosis development (see section "Special instructions ");
- Thrombophlebitis of deep, vein thrombosis or thromboembolic disease in the active phase or recently transferred (deep vein thrombosis, pulmonary embolism), arterial thromboembolic diseases (eg, myocardial infarction);
- Pregnancy;
- lactation period;
- acute or chronic liver disease before normalization of functional liver samples;
- liver cancer;
- congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson and Rotor);
- hemangioma;
- disorders of cerebral circulation in the present or in the anamnesis (ischemic stroke, hemorrhagic stroke);
- Herpes (in the anamnesis);
- ischemic heart disease, atherosclerosis, heart disease, myocarditis;
- porphyria;
- deficiency of lactase, lactose intolerance;
- glucose-galactose malabsorption;
- Hypersensitivity to any of the components of the drug.
With caution: leiomyoma (uterine fibroadenoma), or endometriosis; presence of risk factors for thromboembolism; depression; hyperlipoproteinemia; idiopathic jaundice; (including during the previous pregnancy); arterial hypertension; disease, liver with normal functional tests of the liver, including liver adenoma; diabetes mellitus with, or without diabetic angiopathy; cholelithiasis; migraine or (strong),
headache; systemic lupus erythematosus; endometrial hyperplasia in the anamnesis; fibroadenoma of the breast; estrogen-dependent tumors; mastopathy; ulcerative colitis; kidney failure; epilepsy; bronchial asthma; otosclerosis; chronic heart failure; multiple sclerosis; hypertriglyceridemia; anticoagulant therapy; hypercalcemia, hypokalemia, visual impairment (risk of retinal artery thrombosis); The presence of relatives of the first degree of kinship with breast cancer. The experience of treating women over the age of 65 is limited.
PREGNANCY AND LACTATION
The use is contraindicated.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution in kidney failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in acute or chronic liver disease before the normalization of functional liver tests.
APPLICATION FOR CHILDREN
The drug is not intended for use by children.
APPLICATION IN ELDERLY PATIENTS
Clinical experience in the use of the drug over the age of 65 is not enough.
SPECIAL INSTRUCTIONS
Hormone replacement therapy is designed to treat only those climacteric symptoms that make the patient's daily life difficult. Evaluation of the benefit / risk of treatment with Rheumelid should be carried out throughout the course of treatment, periodic medical examinations should be conducted, the frequency of which is set individually, but at least every 6 months, and which include measurement of blood pressure, examination of mammary glands , abdominal and pelvic organs, gynecological examination (including analysis of the cervical cervical smear and ultrasound to exclude endometrial hyperplasia). Surveys, including mammography, are carried out in accordance with the established order of preventive examination and clinical data of a particular patient.
The drug is administered only to women who have had their last menstruation at least 1 year ago.
The drug is not a contraceptive and does not protect against sexually transmitted diseases.
The drug is not intended for use by children.
Clinical experience in the use of the drug over the age of 65 is not enough.
Conditions requiring immediate discontinuation of treatment:
- jaundice or liver dysfunction;
- significant increase in blood pressure;
- the appearance of a migraine headache;
-pregnancy.
Hyperplasia of the endometrium: the risk of developing hyperplasia and endometrial cancer is higher with prolonged use of estrogens as monotherapy. Periodic, for at least 12 days, during the cycle, an additional appointment
progestogen to women who have not undergone a hysterectomy, significantly reduces the risk of the disease. In the first months of treatment, bleeding from the vagina or spotting can occur. If such bleeding occurs at, later stages of treatment, or continues after discontinuation, a re-examination, possibly with endometrial biopsy, should be performed to exclude malignant neoplasm.
Breast cancer: A randomized, placebo-controlled study of the WHI (Women's Health Initiative) and epidemiological studies, including MWS (Million Women Study), showed that there is an increased risk of developing breast cancer in women taking estrogens, estrogen-progestogen combinations or tibolone in the process of HRT for several years (see the "Side effect" section). In all cases of HRT, the risk becomes evident in the first years of treatment, which increases with the duration of treatment, however, after
cessation of treatment, for several, more often than 5 years, returns to the initial level.
During MWS, the relative risk of breast cancer associated with the administration of conjugated equine estrogens (CEE) or estradiol (E2) was higher when the progestogen was added either sequentially or permanently, regardless of the type of progestogen. The degree of risk was the same, regardless of the route of administration of the drug. In the WHI study, the continuous administration of a combination of conjugated equine estrogen and medroxyprogesterone acetate (CEE + MRA) was associated with breast cancer cases, the number of which was slightly higher, and metastases to local lymph nodes occurred more frequently than in placebo.
In HRT, especially in the combination of estrogen with progestogen, there is an increase in the density of mammograms, which makes it difficult to detect breast cancer.
Venous thromboembolism: HRT is associated with a higher relative risk of venous thromboembolism (VTE). namely, deep vein thrombosis or pulmonary thromboembolism. A two- to three-fold increase in the risk was identified for patients who underwent HRT treatment, compared with those who did not undergo this course of treatment. It has been established that there are 3 cases of VTE for 1000 women aged 50-59 years who did not undergo HRT treatment. which take place over a 5-year period, and at the age of 60-69 years - 8 cases per 1000 women. The estimated number of additional cases of VTE among healthy women aged 50-59 years who received HRT for 5 years is 2-6 (the most accurate estimate = 4) per 1000 women, and at the age of 60-69 years - 5-15 of cases (the most accurate estimate = 9) per 1000 women. The development of VTE is most likely in the first year of HRT, than in the following period.
Recognized risk factors for VTE include the presence of a disease in a personal or family history, severe obesity (body mass index greater than 30 kg / m 2 ), and systemic lupus erythematosus. There is no consensus on the possible role of varicose veins in the development of VTE.
An increased risk of VTE occurs when there is a history of VTE or thrombophilia. HRT may increase the risk. If there is a history of thromboembolism or repeated cases of spontaneous abortion, a patient should be examined to exclude a predisposition to thrombophilia. The appointment of HRT to such women is contraindicated until a thorough assessment of thrombophilic factors or anticoagulant treatment is initiated. It is necessary to carefully weigh the relation
benefit / risk of HRT use in women; who take anticoagulants. The risk of VTE may temporarily increase with prolonged immobilization, extensive trauma or radical surgery. In the postoperative period, careful attention should be given to preventive measures. prevention of cases of VTE. When planning a surgical intervention involving prolonged immobilization of the patient, in particular with abdominal intervention or orthopedic surgery of the lower extremities for 4-6
weeks before surgery, HRT should be suspended as soon as possible. Treatment is not, should be resumed until the woman acquires complete mobility. - If VTE develops after the start of treatment, the drug should be discontinued. Patients should be warned about the need to immediately seek medical help in case of signs of VTE (painful edema of the lower limb, sudden chest pain, shortness of breath).
Cardiac ischemia. Randomized, controlled trials have not revealed any benefits to the cardiovascular system of the continuous use of CEE + MRA. Two large clinical trials, the WHI and HERS (Heart and Estrogen / Progestin Replacement Study), showed the possibility of an increased risk of cardiovascular disease in the first year of combined treatment and the lack of benefits. Data from randomized, controlled trials using other HRT-based drugs to study effects that affect cardiovascular morbidity and mortality are limited. Thus, it remains to be seen whether these data are applicable to other HRT preparations.
Violation of cerebral circulation. The results of a large randomized clinical trial of WHI showed an increased risk of developing cerebral circulation disorders in healthy women who underwent continuous treatment with a combination of CEE + MRA. It has been established that in women who have not undergone HRT, the number of cases of cerebral circulation that may occur during 5 years is approximately 3 per 1,000 women aged 50-59 years and 11 cases per 1000 women aged 60-69 years . In those women who took conjugated estrogens with MPA for 5 years, the number of additional cases of cerebral circulation disorder ranges from 0 to 3 (the most accurate estimate is 1) per 1,000 women aged 50-59 years and 1-9 cases per 1000 women aged 60-69 years (the most accurate estimate = 4).
Data on whether this increased risk for other HRT drugs are unknown.
Cancer of the ovaries. Long-term use (within 5-10 years) of only estrogen preparations with HRT in women with a distant uterus is associated in some epidemiological studies with an increased risk of developing ovarian cancer. It remains unclear whether long-term use of combined HRT increases the risk of ovarian cancer compared to the risk associated with the use of drugs containing only estrogen.
There is no conclusive evidence of improvement in cognitive function. There is a study in the WHI that demonstrates the existence of a risk of developing dementia in women who, after age 65, have started taking a combination drug continuously containing CEE and MRA. It is not known whether this applies to women in younger
postmenopausal age or other HRT preparations.
Other conditions:
- Patients with diseases of the heart and kidneys require careful observation, because estrogens. can, cause; fluid retention in the body. In the terminal stage of renal failure, strict medical control should be ensured in view of the possible increase in plasma concentrations of the active substances of the preparation Revmelid.Treatment of women with estrogen with prior hypertriglyceridemia requires increased caution because of the danger of a significant increase in the concentration of triglycerides; in the blood with subsequent, development, in rare cases,
pancreatitis.
-Estrogens increase the concentration of thyroxine-binding globulin, which leads to an increase in the total, the concentration of circulating thyroid hormones, determined by the content of protein-bound iodine, the concentration of thyroxine (determined by column chromatography or radioimmunological method) or triiodothyronine (determined by radioimmunological method). The concentrations of free thyroxine and triiodothyronine remains unchanged. Mogut rising concentrations of other svyazyvayuschih.belkov serum is including corticosteroid-binding globulin binding globulin sex hormones, which leads to increased concentrations of circulating corticosteroids and sex hormones, respectively. The concentrations of free or biologically active hormone remain unchanged.
The drug is contraindicated in case of intolerance to lactose.
Impact on the ability to drive vehicles and manage mechanisms
Posts on the effects on the ability to drive vehicles and mechanisms of no.
OVERDOSE
Symptoms: nausea, vomiting, bleeding, "cancel." There is no specific antidote.
Treatment: symptomatic.
DRUG INTERACTION
Metabolism estrogens and progestogens may be increased with concomitant use. inducers of microsomal liver enzymes, especially cytochrome P450 isozymes, such as protyvoepilepticheskie means (e.g., phenobarbital, phenytoin, carbamazepine), and antibiotics and antivirals (rifampicin, rifabutin, nevirapine, efavirenz).Preparations containing St. John's wort (Hypericum perforatum), can stimulate the metabolism estrogen and progestogen.
Medicines, funds for general anesthesia, opioid analgesics, anxiolytics; Some antihypertensive drugs, ethanol reduce the effectiveness of estrogens and progestogens.With simultaneous application may require correction dosing regimen hypoglycemic drugs.
TERMS OF RELEASE FROM PHARMACY
On prescription.
TERMS AND CONDITIONS OF STORAGE
Store at a temperature of 15-30 В° C. Keep out of the reach of children! Shelf life - 2 years.
