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Кадсила — Kadcyla (Трастузумаб эмтанзин) 100мг/160мг

Кадсила ( Kadcyla ) трастузумаб 100мг и 160мг Рош , Швейцария

Кадсила — Kadcyla (Трастузумаб эмтанзин) 100мг/160мг

Компания Medical&Pharma предлагает современное противоопухолевое  и самый эффективный аналог в современной линейке препаратов — лекарство Кадсила (Трастузумаб эмтанзин ) , являющийся комбинацией герцептина (трастузумаба) и эмтанзина.  Трастузумаб эмтанзин — это конъюгат моноклонального гуманизированного антитела (IgG1) селективно взаимодействуещего с рецептором человеческого эпидермального фактора роста 2 типа (HER2) и ингибитора полимеризации тубулина DM1 (производное мейтанзина), соединенных друг с другом посредством стабильного тиоэфирного линкера MCC (4-(N-малиенимидометил) циклогексан-1-карбоксилат). Эмтанзин представляет собой комплекс DM1-MCC.

Лекарство выписывают пациенткам с метастатическим HER2-положительным раком молочной железы.

Категория:

Описание

Компания Medical&Pharma предлагает современное противоопухолевое  и самый эффективный аналог в современной линейке препаратов — лекарство Кадсила (Трастузумаб эмтанзин ) , являющийся комбинацией герцептина (трастузумаба) и эмтанзина.  Трастузумаб эмтанзин — это конъюгат моноклонального гуманизированного антитела (IgG1) селективно взаимодействуещего с рецептором человеческого эпидермального фактора роста 2 типа (HER2) и ингибитора полимеризации тубулина DM1 (производное мейтанзина), соединенных друг с другом посредством стабильного тиоэфирного линкера MCC (4-(N-малиенимидометил) циклогексан-1-карбоксилат). Эмтанзин представляет собой комплекс DM1-MCC.

Лекарство выписывают пациенткам с метастатическим HER2-положительным раком молочной железы.

Состав

В одном флаконе содержится:

  • активное вещество: трастузумаб эмтанзин 100 мг/160 мг;
  • вспомогательные вещества: сахароза, янтарная кислота, натрия гидроксид, полисорбат.

Показания

• лечение больных с метастатическим HER2-положительным раком молочной железы, ранее получавших лечение таксаном и трастузумабом, или у которых произошло прогрессирование болезни во время или в течение 6 месяцев после завершения адъювантной терапии;

• адъювантная терапия больных с ранним HER2-положительным раком молочной железы и инвазивной остаточной опухолью после неоадъювантной терапии трастузумабом и таксаном.

Фармакодинамика

Механизм действия

Трастузумаб эмтанзин — это конъюгат моноклонального гуманизированного антитела (IgG1) селективно взаимодействуещего с рецептором человеческого эпидермального фактора роста 2 типа (HER2) и ингибитора полимеризации тубулина DM1 (производное мейтанзина), соединенных друг с другом посредством стабильного тиоэфирного линкера MCC (4-(N-малиенимидометил) циклогексан-1-карбоксилат). Эмтанзин представляет собой комплекс DM1-MCC.

Трастузумаб эмтанзин путем связывания с HER2 попадает в клетку и в лизосомах подвергается протеолитической деградации, что приводит к высвобождению DM1-содержащих цитотоксических катаболитов (главным образом, комплекса лизин-МСС-DM1). Как следствие, конъюгация DM1 с трастузумабом создает селективность цитотоксического действия вещества по отношению к опухолевым клеткам с гиперэкспрессией HER2 и упрощает доставку DM1 внутрь таких клеток.

Механизм действия трастузумаба эмтанзина является совокупностью механизмов действия трастузумаба и DM1.

Трастузумаб эмтанзин, подобно трастузумабу, связывается с доменом IV внеклеточного домена HER2, а также с белком комплемента C1q и с рецепторами Fсγ, тем самым устраняет «слущивание» внеклеточного домена HER2 с поверхности клетки, ингибирует передачу внутриклеточного сигнала по пути фосфатидилинозитол-3-киназы (PI3-K), а также способствует активации антителозависимой клеточно-опосредованной цитотоксичности в клетках с гиперэкспрессией HER2.

DM1, цитотоксический элемент трастузумаба эмтанзина, связывается и подавляет полимеризацию тубулина. За счет цитотоксического действия трастузумаб эмтанзин, как и DM1, создает блокаду клеточного цикла в фазе G2/M, что в итоге приводит к программируемой гибели клеток. По данным результатам in vitro исследований цитотоксичности DM1 было показано, что активность DM1 в 20-200 раз превышает активность алкалоидов барвинка и таксанов.

Структура линкера МСС ограничивает системное высвобождение тубулина DM1 и способствует его направленной доставке в клетку, что подтверждается очень низким содержанием в плазме крови свободного DM1 .

Данные доклинического изучения безопасности

Генотоксичность.

По результатам доклинических исследований показано о наличии у трастузумаба эмтанзина анеугенной и/или кластогенной токсичности.

Репродуктивная токсичность.

Данные свидетельствуют, о наличии эмбриотоксического действия трастузумаба и о потенциальном тератогенном и эмбриотоксическом воздействии DM1.

Влияние на фертильность.

По результатам доклинических исследований показано о наличии риска нарушений фертильности при применении трастузумаба эмтанзина.

Иммуногенность.

Возможно развитие иммунного ответа на препарат Кадсила.

Поскольку частота образования антител к препарату была низкой (в клинических исследованиях у 5.1% пациентов обнаруживались антитела к препарату Кадсила в одной и более временных точках после инфузии), нельзя сделать вывод об их влиянии на фармакокинетику, эффективность и безопасность терапии.

Фармакокинетика

Фармакокинетика трастузумаба эмтанзина при в/в введении каждые 3 нед в дозах 2,4–4,8 мг/кг носит линейный характер. У больных, получавших вещество в дозах 1,2 мг/кг или менее, отмечен более высокий клиренс.

Средняя Cmax трастузумаба эмтанзина в сыворотке крови составляет 83,4 (±16,5) мкг/мл при в/в инфузии препарата в дозе 3,6 мг/кг каждые 3 недели. После в/в инфузии Vd трастузумаба эмтанзина в центральной камере составляет 3,13 литра и приблизительно равно объему плазмы.

Метаболизм.

Трастузумаб эмтанзин предположительно подвергается катаболизму и деконъюгации за счет расщепления в клеточных лизосомах. В in vitro исследованиях на микросомах печени человека было показано, что низкомолекулярный компонент трастузумаба эмтанзина (DM1), в основном, метаболизируется изоферментом CYP3A4 и в меньшей степени изоферментом CYP3A5.

в плазме человека катаболиты трастузумаба эмтанзина, Lys-MCC-DM1, MCC-DM1 и DM1 обнаруживаются в низких концентрациях.

Выведение.

После в/в инфузий трастузумаба эмтанзина у пациентов с метастатическим раком молочной железы с гиперэкспрессией HER2 клиренс трастузумаба эмтанзина составил 0,68 л/день, период полувыведения— приблизительно 4 дня. После многократных в/в инфузий каждые 3 нед аккумуляции трастузумаба эмтанзина не наблюдалось.

Катаболиты трастузумаба эмтанзина в основном выводятся с желчью и в минимальной степени с мочой.

Линейность/нелинейность

Трастузумаб эмтанзин при внутривенном введении каждые 3 недели продемонстрировал линейную фармакодинамику в интервале доз от 2.4 до 4.8 мг/кг; более высокий клиренс имели пациенты, получавшие меньшую или равную 1.2 мг/кг дозу.

На фармакокинетику трастузумаба эмтанзина раса, возраст, пол не влияют.

Нарушение функции почек.

По данным популяционного фармакокинетического анализа нарушение функции почек не влияет на фармакокинетику трастузумаба эмтанзина. Значения фармакокинетических параметров препарата у больных с легкой и средней степенью нарушение функции почек схожи с таковыми у пациентов с нормальной функцией почек. Данные о фармакокинетике у пациентов с тяжелой и терминальной почечной недостаточностью ограничены.

Нарушения функции печени.

Печень является основным органом выведения DM1 и его катаболитов. По данным популяционного фармакокинетического анализа нарушение функции печени не влияет на фармакокинетику трастузумаба эмтанзина. Значения фармакокинетических параметров препарата у больных с легкой и умеренной тяжестью нарушения функции печени схожи с таковыми у пациентов с нормальной функцией печени.

Системные экспозиции (AUC) трастузумаба эмтанзина во время 1-го цикла у больных с легким и умеренным тяжестью нарушения функции печени были приблизительно на 38 и 67% ниже экспозиций у пациентов с нормальной функцией печени соответственно. Во время 3-го цикла экспозиция трастузумаба эмтанзина (AUC) после повторного введения у пациентов с легким или умеренным тяжестью нарушения функции печени было в пределах значений, наблюдаемых у больных с нормальной функцией печени. Исследования трастузумаба эмтанзина у пациентов с тяжелым нарушением функции печени не проводились не изучалась

Фармацевтические характеристики

Лиофилизат от белого до почти белого цвета, в виде пористой массы, уплотненной в таблетку.

Восстановленный раствор: бесцветный или с коричневатым оттенком раствор, прозрачный или слегка опалесцирующий.

Упаковка, срок годности, условия хранения

По 100 мг/160 мг трастузумаба эмтанзина во флаконах из бесцветного стекла 15 мл/20 мл соответственно. Каждый флакон с инструкцией размещен в картонную пачку.

Хранить при температуре 2-8 °C. Не замораживать, хранить в недоступном для детей месте,

Срок хранения 3 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 Кадсила (Трастузумаб эмтанзин) по странам СНГ: Россия, Украина, Кыргызстан (Бишкек), Белоруссия, Узбекистан (Ташкент),
а также можем отправить Кадсила (Трастузумаб эмтанзин) по регионам Казахстана: Нур-Султан (Астана), Шымкент, Талдыкорган, Актау и другие.

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