Active substanceLetrozoleLetrozole
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  • Dosage form: & nbspcoated tablets
    Composition:

    Each tablet contains:

    Active substance: Letrozole - 2.5 mg

    Excipients: Lactose monohydrate (milk sugar) -71.48 mg; corn starch - 9,92 mg; cellulose microcrystalline - 10 mg; sodium carboxymethyl starch - 5 mg; silicon dioxide colloid (aerosil) -0.1 mg; magnesium stearate - 1 mg

    Shell composition:

    Opadrai II: hypromellose (hydroxypropylmethylcellulose), titanium dioxide, lactose monohydrate, macrogol (polyethylene glycol 4000), iron oxide yellow, dye quinoline yellow, iron oxide black - 4 mg.

    Description:

    The tablets covered with a cover of yellow color, round biconcave forms. Two layers are visible on the cross-section.

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

    L.02.B.G.04   Letrozole

    L.02.B.G   Enzyme Inhibitors

    Pharmacodynamics:

    Letrozole selectively inhibits aromatase (an enzyme for the synthesis of estrogens) by highly competitive binding to the subunit of this enzyme, the heme cytochrome P450. It blocks the synthesis of estrogens in both peripheral and tumor tissues.

    In postmenopausal women, estrogens are formed predominantly with the participation of the aromatase enzyme, which turns the androgenes synthesized in the adrenal glands (primarily androstenedione and testosterone) into estrone and estradiol. Daily intake letrozole leads to a decrease in the concentration of estradiol, estrone and estrone sulfate in blood plasma by 75-95% of the original content.The violation of the synthesis of steroid hormones in the adrenal glands is not observed. Suppression of the synthesis of estrogen is maintained throughout the treatment.

    The blockade of the biosynthesis of estrogens does not lead to the accumulation of androgens, which are precursors of estrogens. In patients receiving Extrase, there were no changes in the concentrations of luteinizing and follicle-stimulating hormones in the blood plasma, and no changes in thyroid function were noted.
    Pharmacokinetics:

    Letrozole is quickly and completely absorbed from the gastrointestinal tract (GIT), the average bioavailability is 99.9%. Food slightly reduces the rate of absorption, but it does not have clinical significance, therefore letrozole can be taken regardless of food intake.

    The connection between letrozole and plasma proteins is approximately 60% (mainly with albumin - 55%). The equilibrium concentration is achieved during 2-6 weeks of daily intake of a daily dose of 2.5 mg. Pharmacokinetics is nonlinear. Cumulation with long-term use is not noted.

    Letrozole is largely metabolized by isozymes CYP3A4 and CYP2A6 cytochrome P450 to form a pharmacologically inactive carbinol compound.

    It is excreted mainly by kidneys in the form of metabolites, to a lesser extent - through the intestine. The final half-life (T i/ 2) is 48 hours.

    It is excreted from the plasma by means of hemodialysis.

    The pharmacokinetic parameters of letrozole do not depend on the age of the patient.

    In renal failure pharmacokinetic parameters do not change.

    With a mild violation of liver function (Child-Pugh B) mean values AUC although higher by 37%, but remain within the range of values ​​that are observed in individuals without violations of liver function. In patients with cirrhosis of the liver and severe impairment of its function (Child-Pugh FROM) AUC increases by 95% and T1 / 2 by 187%. However, given the good tolerability of high doses of the drug (5-10 mg / day) in these cases, there is no need to change the dose of letrozole.

    Indications:

    Early stages of breast cancer, cells of which have receptors for hormones, in postmenopausal women, as adjuvant therapy.

    Early stages of breast cancer in postmenopausal women after completion of standard adjuvant therapy with tamoxifen as an extended adjuvant therapy.

    Common hormone-dependent forms of breast cancer in postmenopausal women (first-line therapy).

    Common forms of breast cancer in postmenopausal women (natural or induced artificially) who received previous therapy with antiestrogens.

    Contraindications:

    Hypersensitivity to letrozole or any other component of the drug.

    Endocrine status, characteristic of the premenopausal period.

    Pregnancy, the period of breastfeeding.

    Age to 18 years.

    Carefully:With pronounced violations of the liver and kidneys (creatinine clearance less than 10 ml / min). Before prescribing letrozole, the relationship between the potential risk and the expected effect of treatment should be carefully weighed.
    Dosing and Administration:

    Inside, regardless of food intake.

    The recommended dose of Extrase is 2.5 mg once daily, daily, long-term. If signs of disease progression appear, the use of Extras should be discontinued.

    In elderly patients, dose adjustment is not required.

    Patients with impaired hepatic and / or renal function. In patients with impaired hepatic or renal function (creatinine clearance> 10 ml / min), dose adjustment is not required. Nevertheless, patients with severe impairment of liver function should be under constant supervision.

    Side effects:

    Frequency of occurrence of side effects: very often -> 10%, often -> 1-10%, sometimes -> 0.1% - <1%, rarely -> 0.01-0.1%, very rarely - <0.01%, including individual messages.

    On the part of the digestive system: often - nausea, vomiting, indigestion, constipation, diarrhea; sometimes pain in the abdominal region, stomatitis, dry mouth, increased activity of "liver" enzymes.

    From the central and peripheral nervous system: often - headache, weakness; sometimes - depression, anxiety, drowsiness, insomnia, memory impairment, dysesthesia; rarely - irritability, nervousness, hyperesthesia, hypoesthesia.

    From the hemopoietic system and lymphatic system: sometimes - a leukopenia.

    From the cardiovascular system: sometimes - palpitation, tachycardia, thrombophlebitis, increased blood pressure (BP); rarely - embolism of the pulmonary artery, thrombosis of the arteries, cerebral circulation disorders.

    From the respiratory system: sometimes - shortness of breath.

    From the skin and skin appendages: often - alopecia, excessive sweating, skin rash; sometimes - itchy skin, dry skin, hives.

    From the musculoskeletal system: often - myalgia, arthralgia, ossalgia, arthritis.

    From the sense organs: sometimes - cataract, eye irritation, "blurring" of vision, a violation of taste sensations.

    From the side of the urinary system: rarely - frequent urination.

    On the part of the reproductive system: sometimes - vaginal bleeding, discharge from the vagina, dryness of the vagina.

    Other: very often - paroxysmal sensations of heat ("hot flashes"), often - increased fatigue, asthenia, general malaise, peripheral edema, weight gain; sometimes - hypercholesterolemia, generalized edema, pain in tumor nodes, urinary tract infections; rarely - a fever, thirst, a decrease in body weight.

    Overdose:

    Specific treatments for overdose are unknown. Symptomatic and supportive therapy is indicated.

    Interaction:

    Clinical experience in the use of Extras in combination with other antitumour agents is not currentlyattaching.

    According to the research results in vitro, letrozole suppresses activity of cytochrome P450 isoenzymes - CYP2A6 and CYP2C19 (the latter is moderately). When deciding the importance of these data for the clinic, it is necessary to take into account that the isoenzyme CYP2A6 does not play a significant role in the metabolism of drugs. In experiments in vitro it was shown that letrozole in concentrations 100 times higher than the equilibrium values ​​in plasma, does not have the ability to significantly suppress the metabolism of diazepam (a substrate for CYP2C19). Thus, clinically significant interactions with the isoenzyme CYP2C19 unlikely. Nevertheless, caution should be exercised in the joint use of letrozole and drugs, metabolized predominantly with the participation of the aforementioned isoenzymes and having a narrow therapeutic index.

    Special instructions:

    Patients with severe impairment of liver function should be under constant supervision.

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

    During the treatment period, it is necessary to refrain from engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

    Form release / dosage:Tablets of 2.5 mg.
    Packaging:

    For 10 tablets in a planar cell package.

    30 tablets in a can of polymeric materials.

    Each jar or 1 or 3 contour mesh packages together with the instruction for use is placed in a pack of cardboard.
    Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children.
    Shelf life:

    5 years. Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:Extrasia
    Date of registration:29.02.2012
    The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia
    Manufacturer: & nbsp
    Information update date: & nbsp19.10.2015
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