Описание
Препарат Лартруво представляет собой моноклональное антитело, специфичное к рецептору тромбоцитарного фактора роста альфа (PDGF Receptor-α), играющему главную роль в дифференцировке и пролиферации клеток и развитии онкологических заболеваний. Основное действуеющее вещестов препарата — Оларатумаб.
Препарат Лартруво применяется при лечении распространенной саркомы мягких тканей в составе комбинированной терапии с доксорубицином у взрослых пациентов, которые ранее не получали терапию доксорубицином, и не подлежащих лучевой терапии или радикальному хирургическому лечению.
Состав препарата Лартруво
В одном мл препарата содержится:
- действующее вещество: оларатумаб – 10 мг;
- вспомогательные вещества: глицин, L-гистидин, L-гистидина гидрохлорид моногидрат, маннитол, полисорбат 20, натрия хлорид, вода для инъекций.
Фармакодинамика
Вещество Оларатумаб является антагонистом рецептора a-типа тромбоцитарного фактора роста (PDGFR-α), экспрессируемого стромальными и опухолевыми клетками.
Препарат Лартруво представляет собой таргетное рекомбинантное человеческое моноклональное антитело, относящееся к классу иммуноглобулинов IgG1, способного специфически взаимодействовать с PDGFR-α и ингибирует его связывание с лигандами (PDGF-AA, PDGF-BB и PDGF-CC). В результате этого, в исследованиях in vitro вещество оларатумаб способно ингибировать активацию сигнального пути PDGFR-α в стромальных и опухолевых клетках. Также было определено, что in vivo оларатумаб предупреждает PDGFR-α опосредуемые сигнальные процессы в опухолевых клетках и подавляет рост опухолей.
Иммуногенность
Как и все белковые препараты он потенциально обладает иммуногенностью. Было установлено, в ходе клинических исследований, низкая частота образования как антител к препарату Лартруво, так и нейтрализующих антител.
Фармакокинетика
Всасывание Лартруво
Оларатумаб предназначен только для внутривенных инфузий.
Распределение Лартруво
По данным популяционного анализа фармакокинетики средний объем распределения Лартруво в равновесном состоянии составляет 7,7 л (коэффициент вариации CV = 16 процентов).
Выведение Лартруво
По результатам популяционного анализа фармакокинетики средний клиренс оларатумаба составляет 0,56 л/сутки (CV = 33 процента), а средний период полувыведения (Т1/2) – около 11 дней.
Особые группы пациентов
Возраст, пол и расовая принадлежность, по результатам популяционного анализа фармакокинетики, не оказывают клинически значимого влияния на фармакокинетику препарата Лартруво. Объем распределения и клиренс имеют положительную корреляцию с массой тела.
Пациенты с почечной недостаточностью
Не проводились исследования по оценке влияния почечной недостаточности на фармакокинетику оларатумаба. Клинически значимого отличия клиренса оларатумаба, по результатам популяционного анализа фармакокинетики, у больных с легкой степенью почечной недостаточности (клиренс креатинина 60-89 мл/мин), умеренной степенью почечной недостаточности (клиренс креатинина 30-59 мл/мин) и у пациентов с нормальной функцией почек (клиренс креатинина ≥90 мл/мин) не наблюдалось. Данные относительно применения препарата Лартруво у пациентов с тяжелой степенью почечной недостаточности (клиренс креатинина 15-29 мл/мин) отсутствуют.
Пациенты с печеночной недостаточностью
Не проводились исследования по оценке влияния печеночной недостаточности на фармакокинетику препарата Лартруво. По результатам популяционного анализа фармакокинетики клинически значимого отличия клиренса оларатумаба у больных с легкой степенью печеночной недостаточности (общий билирубин ниже верхней границы нормы и активность аспартатаминотрансферазы (ACT) выше верхней границы нормы или общий билирубин в 1,0-1,5 раза выше верхней границы нормы при любой активности аспартатаминотрансферазы, умеренной степенью печеночной недостаточности (общий билирубин в 1,5-3,0 раза выше верхней границы нормы) и у пациентов с нормальной функцией печени (общий билирубин и аспартатаминотрансферазы≤ верхней границы нормы) не наблюдалось. Результаты относительно использования препарата Лартруво у больных с тяжелой степенью печеночной недостаточности (общий билирубин более чем в 3,0 раза выше верхней границы нормы при любой активности аспартатаминотрансферазы) отсутствуют.
Показания к применению препарата Лартруво
- распространенная саркома мягких тканей в составе комбинированной терапии с доксорубицином у взрослых пациентов, которые ранее не получали терапию доксорубицином, и не подлежащих лучевой терапии или радикальному хирургическому лечению.
Применение при беременности и в период грудного вскармливания
Женщинам детородного возраста рекомендуется избегать наступления беременности во время терапии препарата Лартруво. Пациенток рекомендуется информировать о потенциальном риске для беременности и плода. В период проведения лечения и на протяжении минимум 3 месяцев после введения последней дозы препарата Лартруво женщинам детородного возраста следует использовать эффективные методы контрацепции.
Беременность
Данные о применении препарата Лартруво у беременных женщин отсутствуют. Наблюдались пороки развития плода и костные альтерации в исследовании токсического эффекта антител к мышиному PDGFR-α на репродуктивную функцию и развитие плода у мышей.
Ввиду механизма действия предполагается потенциальный вред препарата для плода. Использование препарата Лартруво не рекомендовано во время беременности, а также женщинам детородного возраста, не использующим контрацепцию.
Период грудного вскармливания
Информация относительно проникновения препарата в грудное молоко отсутствует. Так как человеческий иммуноглобулин IgG проникает в грудное молоко, грудное вскармливание во время терапии препарата и в течение как минимум 3 месяцев после введения последней дозировки не рекомендуется.
Фертильность
Данные о влиянии препарата Лартруво на фертильность человека отсутствуют.
Особые группы пациентов
Пациенты пожилого возраста (старше 65 лет)
Данные относительно использования препарата у пациентов старше 75 лет ограничены. Особые рекомендации относительно снижения дозировки не требуются.
Пациенты с почечной недостаточностью
Исследования использования препарата Лартруво у больных с почечной недостаточностью не проводились. Возможно, согласно данным популяционного анализа фармакокинетики можно предположить, что пациентам с почечной недостаточностью легкой и средней степени тяжести коррекции дозировки не требуется. Данные относительно использования препарата Лартруво у пациентов с почечной недостаточностью тяжелой степени (клиренс креатинина <30 мл/мин) отсутствуют.
Пациенты с печеночной недостаточностью
Исследования использования оларатумаба у больных с печеночной недостаточностью не проводились. Вероятно, согласно данным популяционного анализа фармакокинетики, можно предположить, что больным с печеночной недостаточностью легкой степени тяжести коррекции дозировки не требуется. Данные относительно применения препарата Лартруво у пациентов с печеночной недостаточностью средней степени ограничены. Данные относительно использования препарата Лартруво у пациентов с печеночной недостаточностью тяжелой степени отсутствуют.
Дети и подростки до 18 лет
Эффективность и безопасность оларатумаба при применении у детей и подростков в возрасте до 18 лет не установлены, данные отсутствуют.
Влияние на способность управлять транспортными средствами и работать с механизмами
Препарат Лартруво может оказывать незначительное влияние на способность управлять транспортными средствами и работать с механизмами. Поскольку препарат часто вызывает повышенную утомляемость, пациентам рекомендуется соблюдать осторожность при управлении транспортными средствами или работе с механизмами.
Фармацевтические характеристики препарата Лартруво
Концентрат для приготовления раствора для инфузий. Прозрачного или слегка опалесцирующего, бесцветного или слегка желтого цвета.
Упаковка, срок годности, условия хранения препарата Лартруво
Концентрат для приготовления раствора для инфузий 10 мг/мл.
По 19 мл (190 мг/19 мл) или 50 мл (500 мг/50 мл) препарата упаковано в бесцветный стеклянный флакон типа I, укупоренный резиновой пробкой из хлорбутила, алюминиевой обкаткой и полипропиленовым колпачком.
По одному флакону вместе с инструкцией по применению препарата упакованы в пачке картонной.
Препарат следует хранить при температуре от 2 до 8°С. Приготовленный раствор хранить не более 24 часов при температуре от 2 до 8°С и дополнительно не более 12 часов при комнатной температуре ниже 25°С. Не замораживать и не встряхивать.
Препарат следует хранить в местах, недоступных для детей и хранить в оригинальной упаковке для защиты от света.
Срок годности препарата 2 года. Не применять 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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