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Нерлинкс — Nerlynx (Нератиниб)

Нерлинкс

Нерлинкс — Nerlynx (Нератиниб)

Препарат Нерлинкс применяется для адъювантной терапия рака молочной железы. Основное действующее вещество препарата — Нератиниб — представляет собой ингибитор тирозинкиназы — противораковое вещество, используемое для лечения рака груди.

Препарат Нерлинкс — новый препарат, одобренный FDA к применению в качестве продолжения адъювантной терапии на основе трастузумаба для ранней стадии HER2-положительного рака молочной железы (РМЖ).

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Описание

Препарат Нерлинкс применяется для адъювантной терапия рака молочной железы. Основное действующее вещество препарата — Нератиниб — представляет собой ингибитор тирозинкиназы — противораковое вещество, используемое для лечения рака груди.

Препарат Нерлинкс — новый препарат, одобренный FDA к применению в качестве продолжения адъювантной терапии на основе трастузумаба для ранней стадии HER2-положительного рака молочной железы (РМЖ).

Препарат Нерлинкс относится к фармакотерапевтической группе противоопухолевых средств для лечения рака молочной железы HER2 положительного, адъювантная целевая онкотерапия, которая назначается после курса адъювантной терапии Герцептином после операции.

Четверть пациенток, прошедших хирургическое операционное вмешательство с последующим лечением трастузумабом, сталкиваются с рецидивами. В связи с этим адъювантная терапия крайне важна для достижения устойчивой ремиссии РМЖ.

Для пациентов, страдающих HER2 положительным видом опухоли, препарат Нерлинкс — первое лекарственное средство расширенной терапии, нацеленной на снижение риска рецидива после прохождения основного курса лечения трастузумабом.

Препарат Нерлинкс — противоопухолевый медикамент, ингибитор тирозинкиназ Her2/neu и EGFR. Он ингибирует способность злокачественных клеток получать химические сигналы, оказывающие влияние на рост опухолевых клеток.

Препарат Нерлинкс следует принимать длительно, в течение двух лет после оперативного удаления опухоли груди и курса химиотерапии трастузумабом.

FDA одобрило препарат Нерлинкс, с действующим веществом нератиниб, для продленной адъювантной терапии HER2-положительного рака молочной железы (РМЖ) на ранней стадии. Для пациенток с данным заболеванием — это первый препарат для продленной адъювантной терапии, позволяющий снизить риск рецидива.

Эффективность и безопасность препарата Нерлинкс (нератиниб) изучались в рандомизированном исследовании с участием 2840 пациентов с HER2-положительным раком молочной железы (РМЖ), завершивших терапию трастузумабом не более чем за два года до клинического исследования.

Специалисты определяли время с момента начала испытания до рецидива или смерти по любой причине. Спустя два года терапии у 94,2 процентов пациентов не наблюдалось развития рецидива, и не было зафиксировано смертельного исхода. В группе плацебо этот показатель был равен 91,9 процентов.

Препарат Нерлинкс является таргетной терапией, но в отличие от препаратов Perjeta (Пертузумаб), Герцептина (Трастузумаб), Kadcyla (T-DM1 или Адотрастузумаб Эмтанзин), данное лекарство не имеет иммунный характер антител — это химическое соединение, а не антитело.

Риск рецидива у женщин с ранней стадией рака молочной железы HER2 + может достигать 25 процентов. Препарат Нерлинкс (Нератиниб) снижает риск рецидива и это его основное преимущество: лекарственное средство используется для лечения HER2-положительного рака молочной железы на ранней стадии в течение длительного периода времени после хирургического вмешательства (врачи называют эту терапию — расширенная адъювантная терапия). Пациентка принимает онкопрепарат в течение двух лет после хирургического удаления опухоли груди и курса химиотерапии с включением Герцептина (Трастузумаб).

Механизм действия: вещество Нератиниб является ингибитором тирозинкиназы, который необратимо взаимодействует с рецептором фактора роста эпидермиса человека 2 (HER2) и 4 (HER4), эпидермальным рецептором фактора роста (EGFR). In vitro нератиниб уменьшает аутофосфорилирование EGFR и HER2, подавляет сигнальные пути AKT и MAPK, и проявляет противоопухолевую активность в EGFR и/или HER2, экспрессирующих клеточных линиях карциномы. M3, M6, M7 и M11 — метаболиты нератиниба, ингибировали активность EGFR, HER2 и HER4 in vitro. In vivo пероральное применение нератиниба тормозит рост опухоли в моделях ксенотрансплантата мыши с линиями опухолевых клетoк, экспрессирующих HER2 и EGFR .

Нератиниб не оказывает значимого влияния на интервал QTc.

Фармакокинетика Нерлинкс

Препарат Нерлинкс демонстрирует нелинейный фармакокинетический профиль с меньшим, чем дозозависимое увеличение кривой AUC при повышении суточной дозировки в диапазоне от 40 до 400 мг.

Абсорбция Нерлинкс

Препарат Нерлинкс и его основные активные метаболиты — M3, M6 и M7 — достигают максимальных концентраций после перорального приема в пределах от 2 до 8 часов .

Влияние пищи

Пища с высоким содержанием жиров увеличивает максимальную концентрацию и AUCinf нератиниба в 1,7 (90 процентов ДИ: 1,1-2,7) и 2,2 раза (90 процентов ДИ: 1,4-3,5) соответственно. Стандартная пища увеличивает максимальную концентрацию и AUCinf нератиниба в 1,2 (90 процентов ДИ: 0,97-1,42) и 1,1 раза (90 процентов ДИ: 1,02-1,24), соответственно.

Распределение Нерлинкс

Средний ( процент CV) кажущийся объем распределения нератиниба в равновесном состоянии (Vss/F) составлял 6433 литров (19 процентов). Связывание нератиниба с белками плазмы превышало 99 процентов и не зависило от концентрации. Препарат Нерлинкс преимущественно взаимодействует с человеческим альфа-1-кислым гликопротеином и человеческим сывороточным альбумином.

Элиминация Нерлинкс

После 7 дней приема здоровыми добровольцами 240 мг нератиниба ежедневно, средний период полувыведения (процент CV) нератиниба, М3, М6 и М7 составлял 14,6 (38 процентов), 21,6 (77 процентов), 13,8 (50 процентов) и 10,4 (33 процентов) часов соответственно. Средний период полувыведения нератиниба составлял от 7 до 17 часов после приема одной пероральной дозировки пациентами с раком молочной железы (РМЖ).

Метаболизм

Препарат Нерлинкс главным образом метаболизируется в печени с помощью CYP3A4 и в меньшей степени с помощью флавинсодержащей монооксигеназы (FMO).

Системная экспозиция (AUC) активных метаболитов M3, M6, M7 и M11 составляет 15 процентов, 33 процентов, 22 процентов и 4 процентов

от системной экспозиции нератиниба (AUC) соответственно.

Экскреция

После перорального введения 200 мг (0,83 от рекомендованной суточной дозы) радиоактивно меченого нератиниба, в фекалиях обнаруживается 97,1 процентов, а в моче 1,13 процентов от общей дозировки. 61 процентов введенной радиоактивности выводился в течение 96 часов и 98 процентов через 10 дней.

Применение Нерлинкс

Препарат Нерлинкс показан для адъювантной терапии взрослых пациентов на ранней стадии HER2-положительного рака молочной железы (РМЖ), ранее проходивших лечение трастузумабом.

Применение при беременности и кормлении грудью

Препарат Нерлинкс обладает тератогенным действием, женщины репродуктивного возраста должны использовать эффективные методы контрацепции во время терапии и по крайней мере один месяц после приема последней дозировки нератиниба.

Нератиниб противопоказан при лактации и по меньшей мере один месяц приема последней дозировки нератиниба.

Меры предосторожности

Диарея

Сообщалось о сильной диарее и связанных с ней осложнениях, таких как гипотония, дегидратация и почечная недостаточность, при использовании препарата Нерлинкса. Диарея была зарегистрирована у 95 процентов пациентов, принимавших нератиниб, в рандомизированном плацебо-контролируемом исследовании. В группе нератиниба диарея 3-й степени наблюдалась в 40 процентах случаев, а диарея 4-й степени — у 0,1 процента пациентов. У большинства пациентов (93 процентов) отмечалась диарея в течение первого месяца терапии нератинибом.

Антидиарейная профилактика лоперамидом снижает частоту и тяжесть диареи.

При развитии тяжелой диареи с дегидратацией, при необходимости следует вводить жидкость и электролиты, приостанавливать прием или уменьшать дозу нератиниба.

Гепатотоксичность

Прием нератиниба сопровождается гепатотоксичностью, характеризующейся повышенными ферментами печени. В в рандомизированном плацебо-контролируемом исследовании у 9,7 процентов пациентов наблюдалось превышение аланинаминотрансферазы (АЛТ) ≥ 2 раза верхней границы нормы, у 5,1 процентов пациентов наблюдалось превышение аспартатаминотрансферазы (АСТ) ≥ 2 раза верхней границы нормы, а у 1,7 процентов пациентов наблюдалось превышение и АСТ или АЛТ > 5 раз верхней границы нормы. Гепатотоксичность или увеличение трансаминаз приводили к прекращению приема препарата у 1,7 процентов пациентов, получавших нератиниб.

Общий билирубин, АСТ, АЛТ и щелочную фосфатазу следует оценивать до начала лечения нератинибом, ежемесячно в течение первых трех месяцев лечения, затем каждые 3 месяца или при появлении симптомов гепатотоксичности, таких как нарастание утомляемости, рвоте, тошноте, боль в верхнем правом квадранте живота, лихорадке, сыпи и эозинофилии.

Фармацевтические характеристики

Препарат Нерлинкс выпускается в таблетках в дозировке 40 мг.

Упаковка, срок годности, условия хранения

Препарат Нерлинкс упакован в лекарственную баночку из ПВХ. В каждой баночке 180 штук таблеток. Каждая баночка вместе с инструкцией по применению упакована в картонную пачку.

Хранить препарат Нерлинкс при комнатной температуре.

Срок годности препарата Нерлинкс — 2 года.

 

 

 

Наша компания работает как на территории Казахстана, так и осуществляет доставку в страны ближнего зарубежья. Обращайтесь к нам за консультациями по контактным телефонам.

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Работаем и отправляем Нерлинкс (Нератиниб) по странам СНГ: Россия, Украина, Кыргызстан (Бишкек), Белоруссия, Узбекистан (Ташкент),
а также можем отправить Нерлинкс (Нератиниб) по регионам Казахстана: Нур-Султан (Астана), Шымкент, Талдыкорган, Актау и другие.

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    a halt. Position your dumbbells so that they’re
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    If you want to build an even bigger and stronger rear delt, you want to add
    bent-over lateral raises to your shoulder exercise routine.
    What makes the Stability Ball Cobra so efficient for the rear delts?
    The train requires you to raise your arms against gravity while
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    the rear deltoids intensely as they work to stabilize
    and raise your upper body. When you perform an Incline Dumbbell
    Y Elevate, you’re participating in an upward lifting motion that’s diagonally aligned, identical to the letter ‘Y’.

    This unique angle locations a better demand on your rear deltoids,
    shifting the focus from the more commonly engaged entrance and middle deltoids.

    The upright row is a barbell exercise that works not solely your side delts, but additionally your upper trapezius.
    The stability of the bench will allow you to focus in your front and side delts
    with out worrying as much about stability, though the dumbbells will problem and develop your shoulder stability.
    That’s why we’ve compiled an inventory of the 10 best shoulder exercises for muscle and energy.
    There’s a broad selection of shoulder exercises, every of which delivers totally different
    results and targets different muscle tissue. Similar to
    the bent-over reverse flyes, the lateral raise additionally requires two dumbbells
    which you’ll raise from the middle up to your
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    Quality reps trump every little thing, and don’t worry if you find
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    lateral raise or a cable lateral raise, arm stops proper along side my physique.
    As always, start with a lighter weight, and concentrate on growing your weights or
    reps performed from one week to the next to keep getting larger
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    The greatest dumbbell shoulder workouts use a variety of exercises to hit all three heads of the deltoid.
    Beneath, I will show you what an instance strength day and
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    for other muscle groups like your legs. «We want to be tremendous bang in your buck [when training the shoulders],» says MH fitness director Ebenezer Samuel, C.S.C.S.
    «You need not kill your shoulders.» With the push press,
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    This is as a result of, initially the push press requires power to be generated from the
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    Once the bar is shifting, the deltoids (along with a variety of other
    upper physique muscles) should powerfully have interaction to find a way to lock-out the elbows and efficiently full the raise.

    The key is to concentrate on progressive overload, which suggests steadily increasing your rep rely or the difficulty of these workout routines as
    you get stronger. Cable entrance raises are a really effective, in style anterior deltoid exercise.
    Like most cable workout routines, they keep the
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    The greatest shoulder workouts are those that work all of the muscle tissue of the shoulder utilizing heavy
    presses, compound exercises, and isolation actions to chisel and tone individual muscle teams.

    Together With the shoulder workouts above, along with a great shoulder warm-up and post-workout stretch, will present you with an excellent shoulder workout
    to build measurement. This compound shoulder exercise
    entails pressing a barbell mounted in a landmine, giving the bar
    a set bar path as you press up at a diagonal angle. The Bent-Over Barbell Row shines in its ability to
    engage the posterior deltoids through a compound movement.

    As you row the barbell, the rear delts work vigorously to both stabilize the
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    For athletes and health enthusiasts, robust rear deltoids are
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    Scale again the load to show up the warmth with this DOMS-inducing shoulder-building routine.
    Various the order of workout routines in your routine ensures balanced development and prevents plateaus.
    This method keeps the muscles adapting and enhancing constantly.
    As earlier than, the video above will show you how to do
    cable raises, and the bullet points beneath describe the shape for using
    dumbbells. You prepare shoulders religiously every
    week, however you’re not making progress, you’re continually in ache,
    and you’re able to scrap shoulder work altogether.
    Dumbbell upright rows put your shoulders in an advantageous position to carry heavier weights.
    This is an efficient train when you have muscular imbalances between your proper and left
    sides. Incline lateral raises might really feel a little silly the
    primary time you break them out in the fitness center, but
    their outcomes aren’t one thing you’ll be able to snort
    at. By getting your ft off of the ground and putting your body
    at an angle relative to gravity, you drive your upper body to engage with the exercise more totally.

    After all, they’re engaged in all your urgent strikes, particularly
    inclines. But relatively weak anterior delts can be holding you again from an even bigger chest, so here is a front-delt-focused exercise you should use instead of your regular shoulder routine.
    You can alternate this routine with a extra balanced delt workout (such
    as the mass workout) in your weekly cut up. DirectionsPerform the workout routines as a circuit, completing one set for
    every in sequence without relaxation in between. So you’ll do one set
    of the Y raise, then immediately go on to the lateral increase, rear-delt swing, and so on. Afterward,
    rest two minutes, after which repeat the circuit as quickly as extra.

    Whereas you traditionally carry out this train standing, some
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    With a name like cranium crushers, you know this could be a
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    capable of do them with dumbbells. Plus, this also enables you to play with totally different hand grips to get that selection. As talked about above,
    these two muscular tissues are sometimes overlooked by many new
    lifters that means these guys are severely limiting the dimensions of their arms.

    Drop into a plank place, with your core tight and palms stacked under your shoulders (A), bend your elbows
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    Maintain a dumbbell within the different hand so that it hangs straight
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    Slowly lower the dumbbell back to the beginning position, then repeat.

    After ending all reps with one arm, do the identical on the alternative aspect.
    Many lifters go away their shoulder coaching to likelihood, hoping that a couple
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    And that isolation is the bent-over reverse fly,
    which is the dumbbell model of the reverse pec deck machine.

    Hold a weight plate or pair of dumbbells in front of your physique.
    With minimal motion from your torso and maintain your arms at a
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    arm coaching. Continue on with your deadlifts, this time unlocking your knees (A) to allow your
    quads to assist in the raise. Have Interaction your lats and stand upright, ‘pushing the ground
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    Our train routines are created by figuring out one of the best workouts for muscle growth,
    core power, and overall well being and well-being. It Is
    usually thought-about one of the top workouts to enhance shoulder stability, mobility,
    and general energy. Nevertheless, many lifters mess this train up, so
    take observe of the instructions. In reality, I program the face-pull for each back workouts and shoulder day as a outcome of it trains each, and it’s simply that nice of an train. Now let
    us take a look at the best shoulder workout
    routines and the means to perform them accurately.
    Out of the three deltoids, the lateral deltoid is usually the most underutilized, so be sure
    to’re together with particular exercises that hit it directly.
    Like all other muscle groups, use an array of reps. You may
    discover this surprising, but for a shoulder workout, this typically means utilizing heavier loads.

    Just go to failure on each set, whether it finally ends up being 8 reps,
    5 reps or however many. Instead, adopt the heavy compound/light isolation system for selection and
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    Most lifters tend to emphasize the anterior
    head and pay too little attention to the medial and rear heads.
    Unnecessary to say, this oversight can damage your long-term progress.
    As An Alternative of attempting to lift too heavy, focus
    on retracting the scapula and contracting the target muscle with each rep,
    says Saini. Saini advises experimenting with different grip
    widths to seek out the position that best targets your shoulders and feels most
    comfortable on your joints.
    If you’re not utilizing dumbbells in your shoulder exercise, you need to be.

    Of course, the barbell pushes a heavy weight,
    but dumbbells provide unique benefits when training your
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    ## You Might Also Like

    — Reducing Wrinkles: Top Natural and Medical Solutions
    — Best Face Exercises for a Youthful Appearance
    — How to Choose the Right Skincare Products for Your Face

    ## References

    1. American Academy of Dermatology (AAD) — Sun protection and
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