Описание
Солирис (Экулизумаб) — гуманизированное рекомбинантное моноклональное антитело — Каппа-иммуноглобулин (IgG2/4k), который связывается с белком комплемента (С5) и подавляет активацию комплементопосредованного растворения клеток. Таким образом, вещество восстанавливает биорегуляцию активности комплемента в крови предотвращает избыточную активность терминального комплекса у больных с атипичным гемолитико-уремическим синдромом, где причиной заболевания является генетически обусловленная дисрегуляция системы комплемента, а также предупреждает внутрисосудистый гемолиз у пациентов с пароксизмальной ночной гемоглобинурией.
Данное моноклональное антитело состоит из постоянных участков человеческого иммуноглобулина (Ig) и комплементарно-детерминированных частей иммуноглобулина мыши, встроенных в вариативные области легкой и тяжелой цепей антитела человека. Ээкулизумаб состоит из двух тяжелых цепей, по 448 аминокислот в каждой, и из двух легких цепей, по 214 аминокислот. Молекулярная масса составляет 147870 Да. Экулизумаб производится в культуре клеток линии NS0 миеломы мыши, затем очищается с помощью ионообменной и аффинной хроматографии. В ходе производства субстанции введены также процессы специфичной инактивации и удаления вирусов.
Состав
Водном мл
- экулизумаб 10 мг
- натрия дигидрофосфата моногидрат, натрия гидрофосфата гептагидрат, натрия хлорид, полисорбат, вода д/и.
Показания
препарата Солирис
- пароксизмальной ночной гемоглобинурией (ПНГ). Эффективность экулизумаб подтверждена у больных с гемолизом и сопутствующими клиническими симптомами, характеризующимися о высокой активности заболевания, вне зависимости от потребности в гемотрансфузиях.
- атипичным гемолитико-уремическим синдромом (аГУС).
Фармакодинамика
Экулизумаб обладает высокой аффинностью к С5-компоненту человеческого комплемента, тем самым подавляя его терминальную активность. Из этого следует полная блокировка расщепления компонента С5 на С5а и С5b и образование терминального комплекса комплемента С5b-9. Таким образом, вещество восстанавливает биорегуляцию активности комплемента в крови предотвращает избыточную активность терминального комплекса у больных с атипичным гемолитико-уремическим синдромом, где причиной заболевания является генетически обусловленная дисрегуляция системы комплемента, а также предупреждает внутрисосудистый гемолиз у пациентов с пароксизмальной ночной гемоглобинурией. В то же время, дефицит терминального комплемента сопровождается повышенной частотой развития инфекций инкапсулированными микроорганизмами, в основном, менингококковой инфекции. При этом экулизумаб поддерживает содержание ранних продуктов активации комплемента, нужных для опсонизации микроорганизмов и выведения иммунных сочетаний.
Назначение пациентам экулизумаб одновременно происходит со стабильным и быстрым снижением терминальной активности комплемента. У большинства пациентов ПНГ концентрация экулизумаба в плазме крови порядка 35 мкг/мл довольно для полного ингибирования внутрисосудистого гемолиза, индуцированного терминальной активацией комплемента.
У больных атипичным гемолитико-уремическим синдромом, также блокируется хроническая неконтролируемая активация комплемента на фоне лечения экулизумаб.
У всех пациентов, получавших препарат Солирис в рекомендуемых дозах, отмечалось быстрое и стабильное снижение активности терминального комплекса комплемента. У всех больных аГУС концентрация препарат Солирис в плазме крови около 50–100 мкг/мл достаточна для практически полного ингибирования активности терминального комплекса комплемента.
Фармакодинамическая активность экулизумаба и его концентрации в плазме прямо пропорционально зависимы. Почти полная блокада гемолитической активности отмечалась у большинства больных при поддержании концентрации экулизумаба в плазме крови ≥35 мкг/мл.
Фармакокинетика
Метаболизм
Человеческие антитела в клетках ретикулоэндотелиальной системы под действием лизосомальных ферментов расщепляются до аминокислот и небольших пептидов.
Наличия перекрестной реактивности и признаков репродуктивной токсичностипо результатам экспериментальных исследований не было показано. Канцерогенный потенциал экулизумаба и его генотоксичность и влияние на фертильность у животных не было изучено.
Клиническая эффективность и безопасность
ПНГ
Эффективность и безопасность препарата Солирис у пациентов с ПНГ и признаками гемолиза оценивали в ходе двойного слепого, 52-недельного открытого нерандомизированного исследования (Sheperd, 97 пациентов), плацебо-контролируемого 26-недельного исследования (Triumph, 87 пациентов), а также открытого расширенного исследования, куда были включены больные из первых двух исследований и 11 пациентов из 2-ой фазы исследования.
У больных ПНГ, получавших Экулизумаб, отмечено значительное стабильное снижение (на 86%) внутрисосудистого гемолиза, оцениваемого по активности лактатдегидрогеназы (ЛДГ). В связи с чем, уменьшалась выраженность анемии, что подтверждалось снижением потребности в гемотрансфузиях и стабилизацией содержания уровня гемоглобина. Пациенты отмечали уменьшение слабости и повышение качества жизни. Наблюдалось уменьшение частоты тромбоэмболических осложнений.
аГУС
Эффективность и безопасность Экулизумаб изучалась в процессе проспективных клинических исследований в детской и взрослой популяциях с общим числом 100 пациентов. В исследованиях принимали участие группы: с пациенты с длительно текущим аГУС без явных гематологических проявлений ТМА, а также недавно диагностированным аГУС и признаками ТМА.
В последствии начала терапии Экулизумаб у всех пациентов было достигнуто снижение активности терминального комплекса комплемента. Также отмечалась нормализация количества тромбоцитов (по данным 2-х исследований — у 82 и 90% пациентов соответственно), которая сохранялась в течение двух лет (у 88 и 90% пациентов соответственно). Проводимое лечение приводило к ингибированию комплементопосредованной ТМА и отсутствию симптомов ТМА (у 80 и 88% пациентов соответственно), сохраняющихся на протяжении 2 лет: у 88 и 95% пациентов соответственно.
В процессе терапии препаратом Солирис было замечено значительное улучшение функции почек, которое оценивалось по уровню расчетной скорости клубочковой фильтрации (рСКФ): улучшение рСКФ >15 мл/мин/1,73 м2 наблюдалось в обоих исследованиях у 4 и 53% пациентов соответственно, и сохранялась в течение 2 лет у 59 и 40% пациентов соответственно. Нормализации гематологических показателей достигали 76 и 90% пациентов соответственно, в обоих исследованиях с положительной динамикой в течение 2 лет у 88 и 90% пациентов соответственно.
Выведение
Не проводилось специальных исследований для оценки путей выведения экулизумаба. Экулизумаб из за большой молекулярной массы (148 кД) не экскретируется с мочой в неизмененном виде. Исходя из данных о показаниях клиренса (средний клиренс — 0.31±0.12 мл/ч/кг) периода полувыведения (средний T1/2 – 11.3±3.4 дней) установлено, что равновесное состояние достигается через 49-56 дней.
Зависимость фармакокинетики препарата Солирис отвозраста, расы, пола, функциональной активности почек или печени не изучалась.
Фармацевтические характеристики
Концентрат для приготовления раствора для инфузий прозрачный, бесцветный.
Упаковка, срок годности, условия хранения
В стеклянных флаконах по 30 мл, упакованных вместе с инструкцией в пачки картонные. Препарат хранить в защищенном от света месте, в недоступном для детей, при температуре от 2 до 8°С, не замораживать.
Срок годности – 2.5 года. Не использовать после даты истечения срока годности, указанной 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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Работаем и отправляем Солирис (Экулизумаб) по странам СНГ: Россия, Украина, Кыргызстан (Бишкек), Белоруссия, Узбекистан (Ташкент),
а также можем отправить Солирис (Экулизумаб) по регионам Казахстана: Нур-Султан (Астана), Шымкент, Талдыкорган, Актау и другие.
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