Active substanceExemestanExemestan
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  • Dosage form: & nbspfilm coated tablets
    Composition:

    1 tablet, film-coated, contains:

    active substance exemestane 25.00 mg; Excipients: mannitol 40.40 mg, kopovidone type A 5.30 mg, crospovidone type A 3.30 mg, microcrystalline silicate cellulose 21.30 mg (microcrystalline cellulose 20.87 mg, silicon dioxide colloid 0.426 mg), sodium carboxymethyl starch type A 3, 70 mg, magnesium stearate 1.00 mg; film sheath Advantia Prime White 190100BA01 3.0 mg (hypromellose 6 cP 1,875 mg, macrogol-400 0.375 mg, titanium dioxide (E 171) 0.75 mg).

    Description:round biconvex tablets of white or almost white color, covered with a film membrane. On one side is engraving "25", the other side is smooth.
    Pharmacotherapeutic group:antitumor agent - estrogen synthesis inhibitor
    ATX: & nbsp

    L.02.B.G.06   Exemestan

    Pharmacodynamics:

    Irreversible steroidal aromatase inhibitor, similar in structure to the natural substance androstenedione. In postmenopausal women, estrogens are produced primarily by converting androgens to estrogens under the action of the aromatase enzyme in peripheral tissues.Blocking the formation of estrogen by inhibiting aromatase is an effective and selective method for treating hormone-dependent breast cancer in postmenopausal women. The mechanism of action of exemestane is due to the fact that it irreversibly binds to the active fragment of the enzyme, causing its inactivation. In postmenopausal women exemastane significantly reduces the concentration of estrogens in the serum, starting with before5 mg, with a maximum reduction (more than 90%) achieved with doses of 10-25 mg Have Patients in Postmenopausal Women from diagnosed with cancer The mammary gland, receiving 25 mg daily, the total content of the aromatase enzyme in the body was reduced by 98%. Exemestan does not possess progestagenic and estrogenic activity. Only minor androgenic activity is revealed, mainly when used in high doses. Exemestan does not affect the biosynthesis of cortisol and aldosterone in the adrenal glands, which confirms the selectivity of its action. In this regard, there is no need for replacement therapy with glucocorticoids and mineralocorticoids.When using exemestan, even in low doses, a slight increase in the content of luteinizing hormone (IH) and follicle-stimulating hormone (FSH) in the blood serum is observed, which probably develops on the basis of feedback at the pituitary level: a decrease in the concentration of estrogen stimulates the secretion of gonadotropins in the pituitary gland also women in postmenopausal women.

    Pharmacokinetics:

    Suction. After oral administration exemastane quickly absorbed, mainly from the gastrointestinal tract (GIT). Absolute bioavailability is not established. It is assumed that it is limited to the extensive effect of the first passage through the liver. With a single administration of exemestane in a dose of 25 mg, the maximum concentration in the plasma (Cmah) is 18 ng / ml and is achieved after 2 hours. Simultaneous food intake increases bioavailability by 40%.

    Distribution. Linkage to plasma proteins is approximately 90%. Exemestan and its metabolites do not bind to erythrocytes. At repeated reception of unpredictable cumulation eksemestana it is not observed.

    Metabolism. The process of biotransformation of exemestane is carried out by oxidation of the methylene group in the 6th position under the action ofisoenzyme CYP3A4 and / or reduction of the 17-keto group under the action of aldocode-reductase followed by conjugation. Exemestane metabolism products are either inactive or less active with respect to aromatase inhibition than the parent compound.

    ATExcerpt. The half-life (T1 / 2) is approximately 24 hours. Approximately equal amounts of exemestane (about 40%) are excreted in urine and feces within a week. From 0.1 to 1% is excreted unchanged in urine.

    Pharmacokinetics in special clinical cases. There is no established relationship between systemic exposure of exemestan and age.

    In patients with severe renal insufficiency (creatinine clearance less than 30 ml / min), the systemic effect of exemestan is 2 times higher, however, dose adjustment is not required.

    In patients with moderate or severe hepatic insufficiency, the systemic effect of exemestan is 2-3 times higher, but dose adjustment is not required.

    Indications:

    - Adjuvant therapy for early breast cancer in postmenopausal women with estrogen-positive receptors after the completion of 2-3 years of initial adjuvant therapy with tamoxifen.

    - Common breast cancer in women in natural or induced postmenopausal women with progression of the disease on the background of anti-estrogen therapy.

    Contraindications:

    Hypersensitivity to exemestane or any other component of the drug; pre-menopausal endocrine status; pregnancy; lactation period; age to 18 years.

    Carefully:

    Impaired liver and kidney function.

    Dosing and Administration:

    Inside.

    25 mg once a day, preferably after eating.

    In early breast cancer, treatment with the drug is recommended to continue until the total duration of successive adjuvant hormone therapy reaches 5 years. Treatment of patients with advanced breast cancer is prolonged, in the case of progression of the tumor, therapy should be discontinued.

    With hepatic or renal insufficiency correction of the dose is not required.

    In elderly patients correction of the dose is not required.

    Side effects:

    The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - at least 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%, rarely - not less than 0.01%, but less than 0.1%; very rarely - 0.01%, including isolated cases.

    From the nervous system: very often - headache, insomnia; often - dizziness, carpal tunnel syndrome, anorexia, depression; infrequently - drowsiness.

    From the cardiovascular system: very often - the "tides" of blood to the face.

    On the part of the digestive system: very often - nausea; often - vomiting, abdominal pain, constipation, indigestion, diarrhea.

    From the skin and subcutaneous tissues: very often - increased sweating; often - skin rash, alopecia.

    From the musculoskeletal system: very often - joint and skeletal muscle pain, stiffness of the joints; often - osteoporosis, fractures.

    Other: very often - increased fatigue; often - pain of unspecified localization, peripheral edema; infrequently, asthenia.

    Approximately 20% of patients (especially in patients with initial lymphopenia) experienced a periodic decrease in the number of lymphocytes. However, the average number of lymphocytes in these patients did not change significantly with time, and a concomitant increase in the incidence of viral infections was not observed.

    Sometimes there was an increase in the activity of "hepatic enzymes" and alkaline phosphatase (APF),mainly in patients with liver and bone metastases, as well as in the presence of other liver lesions (it is not established whether these changes are related to the use of exemestane or not).

    According to post-marketing research, adverse reactions from the hepatobiliary system, such as hepatitis (including cholestatic), were noted.

    Overdose:

    A single dose of exemestane, which could cause the appearance of life-threatening symptoms, is not established. The use of a single dose of 800 mg and a daily dose of 600 mg in postmenopausal women with advanced breast cancer was tolerated well.

    Treatment: symptomatic therapy. There is no specific antidote. Control of vital functions is necessary.

    Interaction:

    Exemestane is metabolized by isoenzyme CYP3A4 system of cytochrome P450 and aldoketoreductases and does not inhibit any of the basic isoenzymes of the P450 system. Specific inhibition of the isoenzyme CYP3A4 ketoconazole does not have a significant effect on the pharmacokinetics of exemestane.

    Studies of the interaction of exemestane in a dose of 25 mg with rifampicin at a dose of 600 mg daily showed a decrease in the area under the concentration-time curve (AUC) exemestan by 54% and a decrease in Cmah on 41%.The clinical significance of this interaction has not been studied.

    Joint use with anticonvulsants (phenytoin, carbamazepine), herbal preparations containing St. John's wort, rifampicin may reduce the effectiveness of exemestane.

    Exemestane should be used with caution with drugs metabolized by isoenzyme CYP3 A4 and having a narrow therapeutic window.

    Special instructions:

    The drug Exemestane-Teva should not be given to women with premenopausal endocrine status, therefore, in those cases where it is clinically justified, postmenopausal status should be confirmed by determining the level of LH, FSH and estradiol.

    The drug Exemestane-Teva should not be used simultaneously with estrogen-containing drugs, as they neutralize its effect.

    Exemestane is a significant factor in reducing estrogen, reducing bone mineral density and, correspondingly, increasing the incidence of fractures. Before beginning adjuvant therapy with Exemestan-Teva, patients with osteoporosis or a risk of osteoporosis should receive a densitometry to determine bone mineral density.Despite insufficient data, patients who are at risk for osteoporosis and taking Exemestan-Teva should undergo a thorough examination and, if necessary, begin treatment of osteoporosis.

    Patients in the treatment of exemestane should use adequate methods of contraception.

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

    When treating with Exemestan-Teva, care must be taken when driving vehicles and working with machinery, because unwanted reactions from the nervous system (dizziness, drowsiness) can affect the ability to concentrate and the speed of psychomotor reactions.

    Form release / dosage:

    Tablets, film-coated 25 mg.

    Packaging:

    For 10 tablets in a blister of PVC / PVDC / aluminum foil. For 3 or 6 blisters together with instructions for use in a cardboard box.

    Storage conditions:

    Store at a temperature not exceeding 25 ° C. 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:LP-001708
    Date of registration:18.05.2012
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Representation: & nbspTeva Teva Israel
    Information update date: & nbsp20.10.2015
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