Aromazine® (Aromasin®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceExemestanExemestan
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    • Dosage form: & nbspcoated tablets
    Composition:

    Each tablet contains:

    Active substance: Exemestane 25 mg;

    Excipients: mannitol 26.0 mg, hypromellose 1.50 mg, polysorbate 80 mg 0.125 mg, crospovidone 2,125 mg, silicon dioxide colloid 0.125 mg, microcrystalline cellulose 4,625 mg, sodium carboxymethyl starch 2,375 mg, magnesium stearate 0.625 mg.

    Sugar shell composition: hypromellose 1.81 mg, simethicone emulsion 0.009 mg, macrogol 6000 0.181 mg, magnesium carbonate 1.157 mg, titanium dioxide 3.453 mg, methyl parahydroxybenzoate 0.003 mg, polyvinyl alcohol 0.697 mg, sucrose 30.19 mg;

    (components for giving shine: cetyl ether wax 0.0175 mg, talc 0.01 mg, carnauba wax 0.0225 mg.)

    Composition of ink: shellac, ethanol, isobutanol, iron oxide dye (E 172), titanium dioxide (E 171).

    Description:

    Round, biconvex tablets white or white with a grayish shade of color, covered with sugar shell, labeled "7663" on one side, made with black paint.

    Pharmacotherapeutic group:Antitumor agent - estrogen synthesis inhibitor
    ATX: & nbsp

    L.02.B.G.06   Exemestan

    Pharmacodynamics:

    Exemestane is an irreversible steroid 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 the drug Aromazin® is due to the fact that it binds irreversibly to the active fragment of the enzyme, causing its inactivation. In postmenopausal women, Aromazin® significantly reduces serum estrogen concentration, starting at a dose of 5 mg, with a maximum reduction (> 90%) achieved with doses of 10-25 mg. In postmenopausal patients with breast cancer who received 25 mg of the drug on a daily basis, the total level of the aromatase enzyme in the body decreased by 98%.

    Exemestane does not possess progestogen and estrogenic activity. Only minor androgenic activity is revealed, mainly with the use of high doses.Aromazin® does not affect the biosynthesis of cortisol and aldosterone in the adrenal glands, which confirms the selectivity of the drug. In this regard, there is no need for replacement therapy with glucocorticoids and mineralocorticoids. When the drug is used, even at low doses, a slight increase in the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the blood serum is observed, which is characteristic of the drugs of this pharmacological group and probably develops on the basis of feedback at the pituitary level: a decrease in the concentration of estrogens stimulates the secretion of gonadotropins in the pituitary gland also in postmenopausal women.

    Pharmacokinetics:

    After oral administration exemastane quickly absorbed, mainly from the gastrointestinal tract. Absolute bioavailability of the drug is not established. It is assumed that it is limited to the extensive effect of the first passage through the liver. With a single dose of 25 mg, the maximum plasma concentration, equal to 17 ng / ml, is achieved after 2 hours. Simultaneous food intake increases the bioavailability of the drug at 40 %.

    Pharmacokinetic parameters are linear. The final half-life is approximately 24 hours. 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.

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

    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.

    A marked relationship between the systemic effects of the drug and age is not established.

    In patients with severe renal insufficiency (creatinine clearance <30 ml / min.), The systemic effect of exemestane is 2 times higher, but dose adjustment is not required.

    In patients with moderate or severe hepatic insufficiency, the systemic effect of exemestane is 2 to 3 times higher, however, dose adjustment is not required.

    Indications:

    Common breast cancer in women in natural or induced postmenopause, including the progression of the disease against the background of anti-estrogen therapy, as well as the progression of the disease after repeated use of various types of hormonal therapy.

    Adjuvant therapy for early breast cancer in postmenopausal women with estrogen-positive receptors or an unknown receptor status, after 2-3 years of initial adjuvant therapy with tamoxifen, to reduce the risk of relapse (distant or regional) and contralateral breast cancer.

    Contraindications:

    Hypersensitivity to exemestane or any other component of the drug.

    Premenopausal endocrine status.

    Pregnancy and lactation.

    Carefully:

    Impaired liver or kidney function

    Pregnancy and lactation:

    The use of exemestane during pregnancy is prohibited due to the potential risk to the fetus. The drug should also not be given during breastfeeding.

    Dosing and Administration:

    Inside.

    Adults and patients of advanced age

    The recommended dose is 25 mg once a day, preferably after a meal.

    In patients with 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 a long one.

    When there is evidence of progression of the tumor disease or when contralateral breast cancer appears, treatment with Aromazine® should be discontinued.

    Hepatic or renal insufficiency

    Correction of the dose is not required.

    Children

    It is not recommended for use in children.

    Side effects:

    In general, tolerability of Aromazin® is good; The undesirable effects with the use of the drug at a dose of 25 mg / day are mostly minor or moderately pronounced.

    The following undesirable reactions are distributed according to system-organ classes and frequency: very often (≥1 / 10), often (≥ 1/100, but <1/10) infrequently (≥ 1/1000, but <1/100) , rarely (≥ 1/10 000, but <1/1000).

    Metabolic and nutritional disorders: often - anorexia.

    Disorders from the gastrointestinal tract: very often - abdominal pain, nausea; often - vomiting, diarrhea, constipation, dyspepsia, increased appetite; infrequently - stomach ulcer *.

    Mental disorders: very often - depression, insomnia.

    Disturbances from the nervous system: very often - headache, dizziness; often - anxiety, confusion, carpal tunnel syndrome, paresthesia, hypoesthesia, asthenia; infrequently, neuropathy.

    Heart Disease: often - heart failure; infrequently, myocardial infarction.

    Disturbances from the skin and subcutaneous tissues: very often - excessive sweating; often alopecia, rash, itching, dermatitis.

    Disturbances from musculoskeletal and bone tissue: very often - articular and musculoskeletal pain (including arthralgia, pain in the extremities, back pain, arthritis, myalgia); often - fracture, osteoporosis.

    Disturbances on the part of the organ of sight: often - impaired vision.

    Vascular disorders: very often - increased blood pressure, "hot flashes".

    Disturbances from the liver and bile ducts: very often - increased activity of liver enzymes, increased bilirubin concentration in the blood, increased activity of alkaline phosphatase in the blood.

    Disturbances from the respiratory system, chest and mediastinal organs: often - shortness of breath, cough, bronchitis, sinusitis, pharyngitis, rhinitis, chest pain, upper respiratory tract infections.

    Disorders from the kidneys and urinary tract: often - urinary tract infections.

    Violations of the blood and lymphatic system: often lymphedema.

    General disorders and disorders at the site of administration: very often - pain, fatigue; often - peripheral edema, flu-like syndrome, fever, general weakness, infection.

    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.

    * Most patients had a history of gastric ulcer or received non-steroidal anti-inflammatory drugs.

    Postmarketing research:

    Immune system disorders: infrequently, hypersensitivity reactions.

    Disturbances from the liver and bile ducts: rarely - hepatitis, cholestatic hepatitis.

    Disturbances from the skin and subcutaneous tissues: often - hives; rarely - acute generalized exanthematous pustulosis.

    Overdose:

    A single dose of the drug, which could cause the appearance of life-threatening symptoms, is not established. The use of exemestane in a single dose of up to 800 mg in healthy women and in a daily dose of up to 600 mg in postmenopausal women with advanced breast cancer was well tolerated. There are no specific antidotes.

    Treatment is symptomatic under regular monitoring of vital functions and careful monitoring.

    Interaction:

    Preparations containing estrogens completely neutralize the pharmacological action of exemestane. The drug is metabolized by cytochrome P450 (CYP) 3A4 and aldoketoreductases, and does not inhibit any of the major CYP isoenzymes. The specific inhibition of the CYP3A4 isoenzyme by ketoconazole does not significantly affect the pharmacokinetics of exemestane. Despite the established pharmacokinetic interaction of exemestane with rifampicin, a strong inducer of the isoenzyme CYP3A4, the pharmacological activity of the drug Aromazin® (suppression of estrogens) remains unchanged, so dose adjustment is not required.

    Special instructions:

    Aromasine® should not be prescribed to women with pre-menopausal endocrine status, therefore, in those cases where it is clinically justified, postmenopausal status should be confirmed by determining the levels of LH, FSH and estradiol.

    Aromasine® should not be prescribed concomitantly with preparations containing estrogens.

    In connection with the powerful estrogen-lowering effect of exemestane, a decrease in bone mineral density is possible. Prior to the initiation of adjuvant therapy with exemestane, densitometry is recommended to assess bone mineral density in women with osteoporosis or an increased risk of osteoporosis. During treatment with exemestane, special monitoring of women with osteoporosis with the appointment of appropriate therapy is necessary.

    Due to the high prevalence of severe vitamin D deficiency in patients with early breast cancer, prior to initiation of therapy with an aromatase inhibitor, the concentration of vitamin D in the blood plasma should be determined. When detecting a failure, prescribe medications containing this vitamin.

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

    Patients should be warned about the possibility of drowsiness, asthenia and dizziness during treatment with Aromazin®. If these symptoms occur, patients are advised to refrain from driving and practicing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:The tablets covered with a cover of 25 mg.
    Packaging:

    For 15 tablets in PVDH / PVC blister - PVDH of aluminum foil; 1, 2 or 6 blisters together with instructions for use are placed in a cardboard box.

    Storage conditions:

    At a temperature of no higher than 30 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N011835 / 01
    Date of registration:13.08.2010
    The owner of the registration certificate:Pfizer Italy Sr.L.Pfizer Italy Sr.L. Italy
    Manufacturer: & nbsp
    Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation
    Information update date: & nbsp13.09.2017
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