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Эмплисити — Empliciti (элотузумаб)

Эмплисити

Эмплисити — Empliciti (элотузумаб)

Препарат Эмплисити является человеческим иммуностимулирующим моноклональным иммуноглобулином IgGl антителом, который способен специфически связываться с белком SLAMF_7 (седьмой представитель в семействе сигнальных молекул активации лимфоцитов). Основным действующим веществом препарата является элотузумаб.

Препарат Эмплисити напрямую активирует натуральные киллеры через Fc-рецепторы и SLAMF_7, и тем самым in vitro усиливает их противомиеломную активность. Препарат Эмплисити также связывается с SLAMF_7 на миеломных клетках, что способствует их взаимосвязи с натуральными киллерами и тем самым уничтожению миеломных клеток посредством антитело-зависимой клеточной цитотоксичности. В доклинических исследованиях препарат Эмплисити показал синергетическую активность при совместном использовании с леналидомидом.

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Описание

Препарат Эмплисити является человеческим иммуностимулирующим моноклональным иммуноглобулином IgGl антителом, который способен специфически связываться с белком SLAMF_7 (седьмой представитель в семействе сигнальных молекул активации лимфоцитов). Основным действующим веществом препарата является элотузумаб.

Препарат Эмплисити напрямую активирует натуральные киллеры через Fc-рецепторы и SLAMF_7 , и тем самым in vitro усиливает их противомиеломную активность. Препарат Эмплисити также связывается с SLAMF_7 на миеломных клетках, что способствует их взаимосвязи с натуральными киллерами и тем самым уничтожению миеломных клеток посредством антитело-зависимой клеточной цитотоксичности. В доклинических исследованиях препарат Эмплисити показал синергетическую активность при совместном использовании с леналидомидом.

Состав препарата Эмплисити

1 флакон содержит:

  • активное вещество: элотузумаб в дозировках 340 мг (эквивалентно 300 мг вещества) или 440 мг (эквивалентно 400 мг вещества),
  • вспомогательные вещества: натрия цитрата дигидрат; лимонная кислота моногидрат; сахароза; полисорбат 80.

* Фасовка производится с учетом перезакладки в 40 мг (13,3 процента) для 300 мг и 40 мг (10 процентов) для 400 мг, для гарантированного необходимого полного извлечения указанной дозировки. Извлекаемое количество вещества элотузумаба в одном флаконе — 300 мг и 400 мг соответственно.

Фармакодинамика

Препарат Эмплисити является человеческим иммуностимулирующим моноклональным иммуноглобулином IgGl антителом, который способен специфически связываться с белком SLAMF_7 (седьмой представитель в семействе сигнальных молекул активации лимфоцитов). SLAMF_7 в большом количестве экспрессируется на миеломных клетках в независимости от типа цитогенетических аномалий. SLAMF_7 также экспрессируется на натуральных киллерах, нормальных плазматических клетках и других иммунных клетках, в том числе на моноцитах, В-клетках и дендритных клетках, некоторых Т-клетках . SLAMF_7 не обнаруживается на гемопоэтических стволовых клетках и на клетках здоровых тканей.

Препарат Эмплисити напрямую активирует натуральные киллеры через Fc-рецепторы и SLAMF_7 , и тем самым in vitro усиливает их противомиеломную активность. Препарат Эмплисити также связывается с SLAMF_7 на миеломных клетках, что способствует их взаимосвязи с натуральными киллерами и тем самым уничтожению миеломных клеток посредством антитело-зависимой клеточной цитотоксичности. В доклинических исследованиях препарат Эмплисити показал синергетическую активность при совместном использовании с леналидомидом.

Данные по канцерогенности или мутагенности препарата у животных и человека отсутствуют.

Фармакокинетика

Фармакокинетику препарата Эмплисити изучали у пациентов с множественной миеломой, принимавших препарат в дозировках от 0,5 до 20 мг/кг. Препарат Эмплисити обладает нелинейной фармакокинетикой, клиренс препарата снижается с 17,5 до 5,8 мл/день/кг при повышении дозировки с 0,5 до 20 мг/кг. На основании этого предполагают, что клиренс зависит от взаимодействия с мишенью, это, в свою очередь, приводит к более чем пропорциональному увеличение площади под кривой концентрация-время (AUC).

Распределение

Объем распределения вещества элотузумаба приближается к объему внутрисосудистого пространства и от дозировки препарата не зависит. По данным результатов популяционного фармакокинетического анализа типичное значение объёма центрального распределения составляет 4,04 литра. При введении препарата Эмплисити в дозировке 10 мг/кг, концентрация этого препарата в крови снижается приблизительно до 3 процентов от ранее достигнутой максимальной равновесной концентрации. Было установлено на ксенотрансплантатных мышиных моделях, что максимальная терапевтическая эффективность препарата Эмплисити отмечается при концентрации вещества элотузумаба в плазме крови 70 мкг/мл. У человека использование элотузумаба в дозировке 10 мг/кг обеспечивает достижение равновесной концентрации в плазме крови более 70 мкг/мл.

Вещество элотузумаб обладает нелинейной фармакокинетикой. Клиренс препарата снижается с 17.5 до 5.8 мл/сутки на каждый кг при повышении дозировки с 0.5 до 20 мг/кг. На основании этих данных предполагают, что клиренс препарата зависит от взаимодействия с мишенью, что может приводить к более чем пропорциональному увеличению AUC.

Метаболизм

Метаболизм элотузумаба не охарактеризован. Как предполагается, в процессе катаболизма моноклональные антитела будут деградировать на небольшие аминокислоты и пептиды.

Клиренс препарата Эмплисити возрастает с увеличением массы тела — это является основанием для расчета дозировки на массу тела пациента.

Показания к применению препарата Эмплисити

  • препарат Эмплисити в сочетании с леналидомидом и дексаметазоном показан для применения при лечении пациентов с множественной миеломой, принявших один или несколько предшествующих курсов терапии.

Применение при нарушениях функции печени

Не требуется коррекция дозировки у пациентов с легкой степенью тяжести печеночной недостаточности. Применение элотузумаба при нарушении функции печени средней и тяжелой степени противопоказано.

Применение при нарушениях функции почек

Не требуется коррекция дозировки у пациентов с нарушениями функции почек различной степени тяжести, а также у пациентов, которым требуется в проведении диализа.

Применение у детей

Противопоказано применение у пациентов в возрасте до 18 лет.

Применение у пожилых пациентов

Данных по применению препарата у пожилых пациентов нет.

Применение при беременности и кормлении грудью

Исследований влияния препарата Эмплисити на репродуктивную функцию у животных не проводилось. Исследований применения Эмплисити у беременных женщин не проводилось. Применение элотузумаба при беременности противопоказано. Во время лечения женщинам детородного возраста рекомендуется применение контрацепции.

Комбинированная терапия

Использование препарата Эмплисити в сочетании с леналидомидом может вызывать тяжелые, угрожающие жизни врожденные дефекты. В связи с этим, необходимо придерживаться требований, связанных с предохранением (включая тестирование и контрацепцию) от беременности. Препарат леналидомид проникает как в кровь, так и в сперму пациентов. Поэтому во время лечения как мужчинам, так и женщинам необходимо применять надежные методы контрацепции. Перед использованием комбинированной схемы лечения с леналидамидом необходимо ознакомиться с инструкцией по применению препарата леналидомид.

Применение в период грудного вскармливания

Не проводилось исследований относительно проникновения в грудное молоко женщин в период лактации. Согласно общим данным попадание антител в грудное молоко вероятно. Поэтому, исключить риск для новорожденного при применении препарата в период грудного вскармливания нельзя. Ввиду потенциальной опасности развития серьезных побочных реакций у ребенка, применение препарата Эмплисити противопоказано в период грудного вскармливания.

Влияние на фертильность

Исследований касательно влияния элотузумаба на фертильность не проводилось.

Особые указания

Эмплисити может вызывать развитие инфузионных реакций. Инфузионные реакции были отмечены в клинических исследованиях приблизительно у 10 процентов пациентов, получавших терапию препаратом Эмплисити, леналидомидом и дексаметазоном. Наиболее частыми побочными реакциями были озноб, лихорадка и артериальная гипертензия.

В клинических исследованиях при комбинированной терапии с дексаметазоном и леналидомидом инфузионные реакции 3 степени возникли у 1 процента пациентов. В исследовании комбинированной терапии с леналидомидом и дексаметазоном у 5 процентов пациентов потребовалась приостановка введения препарата Эмплисити ввиду развития инфузионных реакций в среднем на 25 минуте, а у 1 процента пациентов препарат пришлось отменить из-за инфузионных реакций.

В клинических исследованиях с участием больных с множественной миеломой частота возникновения инфекций, включая пневмонию, была выше среди больных , получавших терапию препаратом элотузумабом. Необходимо следить за состоянием пациентов и использовать стандартную схему лечения для терапии инфекционных заболеваний.

Среди пациентов, у которых возникли инфузионные реакции, у 70 процентов (в случае комбинации с дексаметазоном и леналидомидом) они возникали во время введения первой дозировки.

У пациентов, получавших терапию элотузумабом, частота развития вторичных злокачественных новообразований была выше, чем в контрольной группе. Известно, что вторичные злокачественные новообразования связаны с воздействием леналидомида, которое отмечалось в течение более длительного периода времени у больных, принимавших комбинированную терапию элотузумабом, дексаметазоном и леналидомидом, чем среди больных, получавших терапию дексаметазоном и леналидомидом. Необходимо контролировать пациентов на предмет развития вторичных злокачественных новообразований.

Фармацевтические характеристики

препарата Эмплисити

Лиофилизат для приготовления концентрата для приготовления раствора для инфузий

Упаковка, срок годности, условия хранения препарата Эмплисити

По 340 мг или 440 мг активного вещества элотузумаба во флаконе из прозрачного бесцветного стекла типа I, закупоренного бутилрезиновой пробкой с алюминиевым колпачком и с защитной крышкой пластиковой.

По одному флакону вместе с инструкцией по применению помещены в пачку картонную.

Места вскрытия пачки картонной заклеены двумя защитными прозрачными бесцветными стикерами. На среднюю часть каждого стикера нанесен рисунок в виде желтой сетки.

Хранить препарат Эмплисити при температуре от 2 до 8 °С в защищенном от света месте. Не замораживать. Хранить в недоступном для детей месте!

Срок годности 3 года.

 

 

 

 

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

 

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