Описание
Препарат Тарцева (Ерлотиниб) являются противоопухолевым средством. Использование таблеток Тарцевы в терапии при раке легкого и поджелудочной железы улучшает признаки общего ответа и безрецидивной выживаемости пациентов. основное действующее вещество препарата Ерлотиниб — представляет собой сильный ингибитор фермента тирозинкиназы, ответственного за внутриклеточное фосфорилирование рецепторов эпидермального фактора роста HER1/EGFR. Торможение процесса внутриклеточного фосфорилирования HER1/EGFR останавливает рост линий патологических клеток и/или приводит к их гибели.
Состав
- активное вещество в одной таблетке эрлотиниба в дозировке:
- 25 мг в виде эрлотиниба гидрохлорида 27,32 мг эрлотиниб
- 100 мг в виде эрлотиниба гидрохлорида 109,29 мг эрлотиниб
- 150 мг в виде эрлотиниба гидрохлорида 163,93 мг
- вспомогательные вещества: лактозы моногидрат; МКЦ целлюлоза микрокристаллическая; натрия крахмала гликолят; натрия лаурилсульфат; магния стеарат
- оболочка: Опадрай белый (гипромеллоза, гидроксипропилцеллюлоза, титана диоксид, полиэтиленгликоль)
Показания препарата Тарцева
Немелкоклеточный рак легкого
- первая линия лечения немелкоклеточного рака легкого с активирующими мутациями в гене EGFR;
- поддерживающая терапия немелкоклеточного рака легкого при отсутствии прогрессирования заболевания после 4 курсов первой линии химиотерапии на основе препаратов платины;
- немелкоклеточный рак легкого после безуспешного химиотерапевтического лечения.
Рак поджелудочной железы
- первая линия терапии рака поджелудочной железы в комбинации с гемцитабином.
Фармакодинамика
Препарат Тарцева представляет собой сильный ингибитор фермента тирозинкиназы, ответственного за внутриклеточное фосфорилирование рецепторов эпидермального фактора роста HER1/EGFR. Экспрессия HER1 /EGFR отмечается на поверхности как нормальных, так и патологических клеток. На доклинических экспериментах ингибирование фосфотирозина EGFR тормозит рост линий опухолевых клеток и/или приводит их к апоптозу.
Мутации EGFR могут обуславливать процессы постоянной активации пролиферативных и антиапоптотических сигнальных путей в клетках. Отличная эффективность эрлотиниба в отношении торможения EGFR-зависимых сигнальных путей в опухолях, несущих мутацию EGFR, обусловлена прочным связыванием эрлотиниба с АТФ-связывающим участком мутированного киназного домена EGFR. При этом ингибируется каскад сигнальных процессов, в результате чего угнетается пролиферация клеток и запускается внутренний путь клеточного апоптоза.
Фармакокинетика
Всасывание
Эрлотиниб хорошо всасывается после приема внутрь и имеет длительную фазу всасывания, при этом среднее значение TС max в плазме составляет 4 часа. Согласно данным исследования на здоровых добровольцах биодоступность эрлотиниба — 59%, прием пищи может увеличивать его биодоступность.
После всасывания в крови эрлотиниб на 95% находится в связанном положении, прежде всего с белками плазмы крови (альбумин и альфа 1- кислым гликопротеинами). Свободная фракция составляет приблизительно 5%.
Распределение
Максимальная концентрация в плазме — 1,995 нг/мл. Равновесная концентрация достигается на 7–8-й день. Перед приемом очередной дозы средняя минимальная концентрация эрлотиниба в плазме крови — 1,238 нг/мл. AUC в интервале между дозами при достижении равновесной концентрации составляет 41,3 мкг·ч/мл.
Кажущийся объем распределения равен 232 л с распределением в ткань опухоли. В образцах опухолевой ткани человека на 9 день лечения эрлотинибом в дозе 150 мг/сут средняя концентрация эрлотиниба равна 1.185 нг/г, что составляет 63% от максимальной концентрации в плазме в равновесном состоянии. Концентрация основных активных метаболитов в ткани опухоли 160 нг/г, что соответствует 113% Cmax в плазме в равновесном состоянии. Сmax в ткани составляет около 73% концентрации препарата в плазме, Tmax в ткани — 1 ч.
Объединение с белками плазмы (альбумин и альфа-1 кислый гликопротеин) составляет почти 95%.
Метаболизм
В основном Эрлотиниб метаболизируется изоферментами цитохрома Р450, в особенности в большей степени при участии изофермента CYP3A4 и в меньшей степени CYP1A2.
Внепеченочный метаболизм с помощью изофермента CYP1А1 в легких, изофермента CYP1B1 в ткани опухоли, изофермента CYP3A4 в кишечнике обеспечивает метаболический клиренс эрлотиниба. Исследования in vitro свидетельствуют о том, что 80-95% эрлотиниба метаболизируется при участии изофермента CYP3A4.
Метаболизм происходит тремя способами:
- О-деметилированием одной из боковых или обеих цепей с дальнейшим окислением до карбоновых кислот;
- окислением ацетиленового участка молекулы с дальнейшим гидролизом до акрилкарбоновой кислоты;
- ароматическим гидроксилированием фенилацетиленового участка молекулы.
В результате О-деметилирования образуются основные метаболиты одной из боковых цепей, обладающие активностью, сходной с эрлотинибом в доклинических экспериментах на моделях опухолей in vitro и in vivo. Они присутствуют в плазме в концентрациях, которые составляют <10% концентрации эрлотиниба, их фармакокинетика аналогична фармакокинетике эрлотиниба.
Выведение
Метаболиты и следовые количества эрлотиниба выводятся, преимущественно, с желчью (>90%), почками выводится небольшое количество перорально введенной дозы.
Клиренс
При монотерапии Тарцева средний период полувыведения 36,2 часа, а средний клиренс 4,47 л/час. Следовательно, ожидается, что Css будет достигнута на 7-8 день. Не установлено существенной связи между клиренсом, возрастом, массой тела, полом и расой больного.
Фармакокинетика препарата зависела от таких показателей, как: альфа 1-кислого гликопротеина, концентрации общего билирубина и курения в настоящий период. Уменьшение клиренса эрлотиниба замечено при увеличении альфа 1-кислого гликопротеина и концентрации общего билирубина — у курильщиков.
Одновременное применение гемцитабина не влияло на клиренс эрлотиниба.
Фармакокинетика у особых групп пациентов
Специальные исследования у детей и пожилых пациентов не проводились.
Нарушение функции печени
В основном Эрлотиниб выводится c желчью. Экспозиция к эрлотинибу у больных с печеночной недостаточностью средней тяжести и больных с нормальной функцией печени одинакова, включительно с пациентами с раком печени 1 стадии или метастазами в печень. Не изучалась фармакокинетика эрлотиниба у больных с тяжелой печеночной недостаточностью.
Нарушение функции почек
В незначительных количествах Эрлотиниб и его метаболиты выводятся почками — менее 9% однократной дозы. Не проводились исследования у пациентов с нарушением функции почек.
Курение
У курильщиков примерно на 24% повышается клиренс эрлотиниба, а по сравнению с пациентами, которые не курят. Экспозиция к эрлотинибу при этом меньше примерно раза в три. Вместе с тем значение равновесной концентрации эрлотиниба у курильщиков показывает примерно в 2 раза более меньших, чем у некурящих. Что объясняется увеличением уровня ферментов CYP1А2 в печени и CYP1А1 в легких. Повышение дозы препарата в 2 раза (со 150 мг в день до 300 мг) позволяет достичь у курильщиков концентраций эрлотиниба, сходной с таким показателем у некурящих.
Фармацевтические характеристики
Таблетки, покрытые пленочной оболочкой, круглой формы, двояковыпуклые. Цвет таблеток: белого или белого с желтоватым оттенком.
Таблетки представлены в дозировке по:
- 25 мг. Имеют на поверхности таблетки логотип и маркировку оранжевого цвета «TARCEVA 25»;
- 100 мг. Имеют на поверхности таблетки логотип, а также маркировку серого цвета«TARCEVA 100»;
- 150 мг. Имеют на поверхности логотип и коричневую маркировку «TARCEVA 150»;
Упаковка, срок годности, условия хранения
По 10 таблеток в блистер из ПВХ/Аl. По три блистера вместе с инструкцией по использованию упакованы в пачку картонную. На пачку нанесена наклейка защитная голографическая, с целью контроля первого вскрытия.
Хранить при температуре не выше 30°С, в недоступном для детей месте.
Срок годности — 4 года. Не использовать по истечении срока годности, указанного на упаковке.
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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