Active substanceMedroxyprogesterone + EstradiolMedroxyprogesterone + Estradiol
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  • Divina
    pills inwards 
  • Individual
    pills inwards 
  • Dosage form: & nbsppills
    Composition:

    Individual 1 mg + 2.5 mg:

    in 1 tablet of estradiol valerate

    1 mg


    medroxyprogesterone acetate excipients q.s.

    2.5 mg

    Individual 1 mg + 5 mg:

    in 1 tablet of estradiol valerate

    1 mg


    medroxyprogesterone acetate

    5 mg

    Excipients

    q.s.

    Individual 2 mg + 5 mg:

    in 1 tablet of estradiol valerate

    2 mg


    medroxyprogesterone acetate

    5 mg


    Excipients

    q.s.

    Excipients: lactose monohydrate, corn starch, gelatin, magnesium stearate.

    Description:

    Individual 1 mg + 2.5 mg: Round flat with bevelled edge of white tablets and code "1 + 2,5" on one side.

    Individual 1 mg + 5 mg: Round flat with a bevelled edge of white tablets and code "1 + 5" on one side.

    Individual 2 mg + 5 mg: Round flat with a bevelled edge of white tablets and code "2 + 5" on one side.

    Pharmacotherapeutic group:Anti-climacteric (estrogen + progestogen)
    ATX: & nbsp

    G.03.F.A.12   Medroxyprogesterone and estrogen

    Pharmacodynamics:

    Estradiol valerate is an ester of natural estrogen - estradiol. Pharmacological effects of estradiol are mediated by binding to specific receptors of estrogens in target tissues. The steroid-receptor complex binds to cellular DNA and stimulates the synthesis of specific proteins. Medroxyprogesterone acetate is a derivative of natural progesterone-17-alpha-hydroxy-6-methylprogesterone. Medroxyprogesterone acetate binds to progestin-specific receptors and acts on the endometrium, transferring it from the proliferative to the secretory phase.

    Estradiol stimulates the proliferation of the endometrium, while increasing the risk of endometrial hyperplasia and cancer. Medroxyprogesterone acetate counteracts this effect.

    Estradiol prevents the development of postmenopausal osteoporosis by reducing the resorption of bone mass. This effect depends on the dose of the drug. In postmenopausal women, a dose of 1 mg has a lesser effect on bone mineral density (BMD) of the vertebrae than a 2 mg dose.

    In addition, the effect on the serum lipid spectrum was shown.In clinical trials, the level of total cholesterol (OX) and low-density lipoprotein cholesterol (LDL-C) was reduced in clinical trials, and the high-density lipoprotein (HDL-C) cholesterol level was increased and the HDL / OX ratio was improved. Estrogen therapy can lead to an increase in the level of triglycerides of the plasma, which in some cases contributes to the development of pancreatitis and other complications in patients with congenital defects in lipoprotein metabolism.

    The individual is a drug for long-term continuous combined hormone replacement therapy (HRT), which is prescribed in order to avoid regular withdrawal bleeding associated with cyclic or sequential HRT. In the first months of treatment, breakthrough vaginal bleeding and menstrual bleeding can sometimes occur, which eventually decrease and cease. 10-12 months after the start of treatment, 90% of women who received 1 mg of estradiol valerate and about 80% of women who received 2 mg of estradiol valerate reach amenorrhea.

    Pharmacokinetics:

    After oral administration estradiol valerate is absorbed from the gastrointestinal tract (GIT) and is rapidly hydrolyzed to estradiol with the help of esterases. The maximum concentration of estradiol in plasma is reached in 4-6 hours. Circulating estradiol binds to plasma proteins, mainly with sex hormone binding globulin, and serum albumin.

    Estradiol undergoes intensive biotransformation. Its metabolites are excreted by the kidneys with urine in the form of glucuronide and sulfate conjugates. Unchanged estradiol is displayed in small quantities. A small part of the dose is excreted by the intestine.

    The absorption of medroxyprogesterone acetate after oral administration is low due to its poor solubility and is subject to wide individual fluctuations. The effect of the first passage through the liver is actually not characteristic of medroxyprogesterone acetate. After oral administration of a single tablet of Individual, the maximum concentration of medroxyprogesterone acetate in plasma is reached within 1-2 hours. Medroxyprogesterone acetate binds to plasma proteins by more than 90% (mainly with albumin).When taken orally, the half-life of medroxyprogesterone acetate is about 24 hours. Medroxyprogesterone acetate is subjected to intensive metabolism in the liver by hydroxylation and conjugation. Medroxyprogesterone acetate is excreted in the urine and bile. Metabolism is not well understood, and the pharmacological activity of metabolites is not known.

    Indications:Hormone replacement therapy (HRT) with symptoms of estrogen deficiency and prevention of osteoporosis in women with a nonoperated uterus that have been in the postmenopausal period for more than three years.
    Contraindications:

    - Identified hypersensitivity to any of the components of the drug.

    - Breast cancer - established, suspected or available in history.

    - Estrogen dependent malignant tumors - suspects or history (eg, endometrial cancer).

    - Uterine bleeding of unclear etiology.

    - Untreated hyperplasia of the endometrium, endometriosis.

    - Deep vein thrombosis, thromboembolism of the branches of the pulmonary artery, as well as other confirmed or existing history of venous thromboembolism.

    - Angina pectoris, myocardial infarction, as well as other established or existing history of arterial thromboembolism.

    - Congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson, Rotor).

    - Acute liver disease or liver disease in history before normalization of laboratory parameters of liver function.

    - An established or presumptive pregnancy, lactation.

    - Severe renal insufficiency.

    - Porphyria, sickle-cell anemia, pituitary tumors.

    Carefully:Multiple sclerosis, lupus syndrome, epilepsy and epileptic syndrome, diabetes mellitus with vascular complications, benign breast, arterial hypertension (resistant to therapy), chronic renal failure, chronic heart failure, bronchial asthma, otosclerosis with complications during previous pregnancy, estrogen-dependent tumors in the anamnesis, cholelithiasis, expressed obesity (including in the anamnesis), migraine.
    Pregnancy and lactation:Contraindicated in pregnancy and lactation.
    Dosing and Administration:

    The drug is prescribed for 1 tablet daily inside without a break. Tablets should be taken at about the same time of day.

    It is recommended to begin treatment with Individual 1 mg tablets + 2.5 mg tablets. Depending on the clinical effect of the treatment, the dosage can be adjusted. Medroxyprogesterone acetate in an amount of 2.5 mg is usually sufficient to prevent breakthrough bleeding. In the event that the bleeding of the breakthrough has begun and continues, and the pathology of the endometrium has been ruled out, the dose of medroxyprogesterone acetate can be increased to 5 mg (Individual 1 mg + 5 mg tablets).

    If 1 mg of estradiol valerate is not enough to alleviate the symptoms of estrogen deficiency, the dose may be increased to 2 mg (Individual 2 mg + 5 mg tablet).

    For maintenance therapy, the lowest effective doses should be used. Treatment with the drug Individual can begin any day if a woman with amenorrhea has not previously received HRT or if the woman received another combination drug for HRT in a continuous regime. In the event that a woman previously received HRT in a cyclic mode, Indiana should begin treatment within a week after the end of the next cycle of HRT.

    Tablets are taken regularly 1 time per day.If one tablet is not taken on time, it should be taken as soon as possible. In case of delay in taking the drug for more than 12 hours, the missed tablet is not taken. Passing the next dose can cause breakthrough uterine bleeding.

    Side effects:

    In clinical studies (as the most frequent undesirable effect) in the treatment Indivinoy described sense voltage mammary occurring less frequently at a dose of 1 mg of estradiol valerate. At the beginning of treatment, there may be spotting from the vagina, but they usually decrease and stop when the treatment continues. Bloody discharge is more common in those cases when the treatment started within 2 first years after the onset of menopause.

    From the nervous system: headache; mood changes, including anxious and depressed mood; dizziness; migraine; sleep disorders.

    From the digestive systemNausea, abdominal pain, dyspepsia, vomiting, flatulence, diarrhea or constipation, rarely - cholecystitis, cholelithiasis, pancreatitis.

    From the side of the cardiovascular system: increased blood pressure, rarely - thrombosis, a feeling of palpitations.

    From the genitourinary system: vaginal candidiasis.

    From the endocrine system: alopecia, hirsutism, engorgement of the mammary glands, an increase in myomatous nodes.

    Allergic reactions: a rash, itching, erythema multiforme, nodal erythema, very rarely - chloasma.

    Other: uterine bleeding, fluctuations in body weight, peripheral edema, changes in libido, cramps in the muscles of the lower limbs, impaired vision, ossalgia increase in blood plasma activity of hepatic transaminases (ALT and ACT), alkaline phosphatase, bilirubin, gamma-glutamyltransferase, lupus erythematosus.

    Overdose:Overdose of estrogen can cause nausea, headache and uterine bleeding. Judging by the numerous reports of mistaken admission of high-dose estrogen-containing oral contraceptives to young children, it does not cause serious adverse effects. Treatment of an overdose of estrogens is symptomatic. High doses of medroxyprogesterone acetate (MPA), used in oncology, do not lead to serious undesirable effects.
    Interaction:

    The drug reduces the effectiveness of antihypertensive drugs, oral anticoagulants and oral hypoglycemic drugs.

    Inductors of microsomal oxidation (incl. phenytoin, barbiturates, hydantoin, antiepileptic drugs, tetracyclines, griseofulvin, rifampicin, ampicillin) reduce the estrogenic effect; LS, suppressing microsomal oxidation (incl. ketoconazole, ciclosporin), - increase.

    Special instructions:

    Before starting or re-appointing HRT, you must collect a complete personal and family history, and conduct a thorough general and gynecological examination to identify possible contraindications and observe the necessary precautions when taking the drug. During the treatment it is also recommended to conduct additional examinations. The frequency of examinations and the methods used are determined for each individual patient individually. Breast examination and / or mammography are conducted in accordance with accepted standards.

    The use of estrogens can affect the results of the following laboratory tests: determination of glucose tolerance, examination of the functions of the thyroid and liver.

    For women receiving HRT, it is necessary to periodically carefully assess the relationship between risk and benefit from such treatment.

    Particular care must be taken to weigh the benefits of treatment and the possible risk from it, if present, have ever occurred before and / or occurred during pregnancy or previous courses of hormone therapy states described in "With caution."

    Patients with heart failure and impaired renal function should be under special control; Estrogens can cause fluid retention. Patients in the terminal stage of kidney disease need special attention, since an increase in the levels of active substances in the blood should be expected.

    Some patients receiving estrogen / progestogen therapy may experience changes in glucose tolerance. Patients with diabetes should closely monitor blood glucose levels in the first months of HRT.

    Data from epidemiological studies suggest that substitution hormone therapy is associated with a relatively high risk of developing deep vein thrombosis in the lower limbs or thromboembolism of pulmonary vessels.Risk factors for the development of thromboembolic diseases are: their presence in a personal and family anamnesis, pronounced obesity (body mass index> 30 kg / m2) and systemic lupus erythematosus. There is no consensus on the possible role of varicose veins.

    The appointment of HRT to patients with recurrent or with established deep vein thrombosis in the lower extremities in history, receiving anticoagulant therapy, requires a careful assessment of the relationship of risk and benefit from HRT. To exclude a predisposition to thrombosis, a history of recurrent thrombosis or recurrent spontaneous abortions should be carefully studied. Prior to the formulation of the above diagnosis or the initiation of anticoagulant therapy, the appointment of HRT should be considered contraindicated.

    The risk of developing deep vein thrombosis in the lower extremities may temporarily increase with prolonged immobilization, extensive injuries or extensive surgical operations. In all postoperative patients, increased attention should be paid to preventive measures aimed at preventing thromboembolic complications after surgical interventions.In cases where prolonged immobilization is necessary after surgical operations, in particular after abdominal surgery and orthopedic operations on the lower limbs, consideration should be given to the temporary discontinuation of HRT 4 to 6 weeks before surgery. The decision to resume HRT is taken individually for each specific case.

    If thrombosis develops after the onset of HRT, the individual should be discarded. Patients should be instructed about the need to seek immediate medical attention if the following symptoms occur: pain and swelling of the lower extremities, sudden pain in the chest, indigestion. The data of epidemiological studies show a slight increase in the likelihood of developing breast cancer in women who received or are currently receiving HRT. The detection of breast cancer may be associated with early diagnosis, the biological effects of HRT, or a combination of both. The likelihood of diagnosing breast cancer increases with the duration of treatment and returns to normal five years after discontinuation of HRT.

    In postmenopausal women receiving estrogen, the risk of cholelithiasis increases.

    Also, when taking HRT, the risk of developing systemic lupus erythematosus increases. The use of estrogens can affect the results of certain laboratory indicators (activity of hepatic transaminases ALT and ACT, alkaline phosphatase, gamma-glutamyltransferase).

    Breakthrough uterine bleeding and unexpressed menstrual bleeding can occur during the first months of treatment. If, despite the adjustment of the dose, such bleeding does not stop, the drug should be discontinued until the cause of bleeding is established. If bleeding recurs after a period of amenorrhea or continues after withdrawal of treatment, its etiology should be established. This may require an endometrial biopsy.

    The experience of treating women over 65 is limited.

    Effect on the ability to drive transp. cf. and fur:

    Does not affect.

    Form release / dosage:Tablets: 1 mg + 2.5 mg; 1 mg + 5 mg; 2 mg + 5 mg.
    Packaging:

    For 28 tablets in a contour mesh calendar pack of PVC / PVDC film and aluminum foil (blister).

    For 1 or 3 blisters with instructions for use in a cardboard bundle.

    Storage conditions:

    Store at temperatures not higher than + 30 ° C in the original packaging.

    Keep out of the reach of children!

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N016341 / 01
    Date of registration:09.11.2007
    Expiration Date:Unlimited
    Date of cancellation:2016-10-17
    The owner of the registration certificate:Orion Corporation Orion Pharma Orion Corporation Orion Pharma Finland
    Representation: & nbspORION CORPORATION ORION PHARMA ORION CORPORATION ORION PHARMA Finland
    Information update date: & nbsp31.10.2017
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