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Абаджио — Aubagio (Терифлуномид)

Абаджио

Абаджио — Aubagio (Терифлуномид)

Препарат Абаджио — это иммуносупрессивный препарат, предназначенный для лечения рассеянного склероза. Основное действующее вещество препарата — Терифлуномид. Он приостанавливает процессы деления некоторых клеток иммунной системы, вероятно тем, что снижает количество циркулирующих Т-клеток и В-клеток —типы белых кровяных телец, вовлеченные в процессы рассеянного склероза. Кроме того, вероятно, терифлуномид обладает иммуномодулирующим и противовоспалительным действием.

Категория:

Описание

Препарат Абаджио — это иммуносупрессивный препарат, предназначенный для лечения рассеянного склероза. Основное действующее вещество препарата — Терифлуномид. Он приостанавливает процессы деления некоторых клеток иммунной системы, вероятно тем, что снижает количество циркулирующих Т-клеток и В-клеток —типы белых кровяных телец, вовлеченные в процессы рассеянного склероза. Кроме того, вероятно, терифлуномид обладает иммуномодулирующим и противовоспалительным действием.

Состав Абаджио

1 таблетка содержит:

  • Активное вещество: Терифлуномид 14 мг.
  • Вспомогательные вещества:
  • Ядро: крахмал кукурузный, лактозы моногидрат, целлюлоза микрокристаллическая, натрия крахмалгликолят, гидроксипропилцеллюлоза, магния стеарат.
  • Пленочная оболочка: смесь для системы покрытия пленочной оболочкой Opadry Blue (гипромеллоза, титана диоксид, тальк, макрогол, алюминиевый лак индигокармина).

 

Показания препарата Абаджио

  • лечение взрослых пациентов с рецидивирующе-ремиттирующим рассеянным склерозом.

Фармакодинамика

Терифлуномид — иммуномодулирующий вещество с противовоспалительными свойствами, обратимо и селективно ингибирующий митохондриальный фермент дигидрооротатдигидрогеназу, который необходим для синтеза de novo пиримидина. Таким образом, терифлуномид блокирует пролиферацию лимфоцитов, для которых необходим синтез пиримидина. Точный механизм действия терифлуномида до конца не изучен, но может быть обусловлен уменьшением количества циркулирующих лимфоцитов.

Иммунная система

В ходе плацебо-контролируемых исследований о влиянии на количество иммунных клеток в крови приема терифлуномида в дозе 14 мг один раз в день было показано, что в среднем это приводило к незначительному снижению количества лимфоцитов, менее чем на 0,3 х 10 процентов, что было отмечено в течение первых 3-х месяцев лечения. Достигнутые уровни сохранялись до окончания лечения.

Влияние на интервал QТ

Терифлуномид в ходе плацебо-контролируемого исследования, проведенного с участием здоровых добровольцев, по сравнению с плацебо, при средних равновесных концентрациях не продемонстрировал потенциала к удлинению интервала QTcF .

Воздействие на канальцевые функции почек

Было отмечено в ходе плацебо-контролируемых исследований более выраженное снижение концентраций мочевой кислоты в сыворотке в диапазоне от 20 до 30процентов у пациентов, принимавших терифлуномид, по сравнению с плацебо. Среднее снижение содержания фосфора в сыворотке составило около 10 процентов в группе герифлуномида по сравнению с плацебо. Считается, что такие эффекты не связаны с изменениями в клубочковых функциях, но связаны с увеличением канальцевой экскреции.

Фармакокинетика

Всасывание

Среднее Тmax в плазме составляет от 1 до 4 ч при перорального приеме терифлуномида и с высокой биодоступностью (приблизительно 100процентов).

Пища не оказывает клинически значимого эффекта на фармакокинетику терифлуномида. На основании средних фармакокинетических параметров, рассчитанных на основании анализа популяционной фармакокинетики с использованием данных о пациентах с рассеянным склерозом и здоровых добровольцах, отмечается медленное достижение равновесной концентрации (приблизительно 100 дней до достижения 95процентов равновесных концентраций), а ожидаемое значение аккумуляции AUC превышает исходное приблизительно в 34 раза.

Распределение

Терифлуномид активно связывается с белками плазмы (> 99процентов) вероятно, с альбумином и, в основном распределяется в плазме. Объем распределения после однократного внутривенного введения препарата 11л.

Биотрансформация

Терифлуномид умеренно метаболизируется. Является единственным веществом, определяемым в плазме. Основной путь биотрансформации терифлуномида представляет собой гидролиз с окислением. Вторичные пути включают окисление, N-ацетилирование и сульфатную конъюгацию.

Выведение Абаджио

Вещество выделяется в основном через желудочно-кишечный тракт, с желчью, в неизменном виде. Терифлуномид — это субстрат эффлюксного переносчика белка резистентности рака молочной железы, который может быть вовлечен в прямую секрецию. В течение 21 дня 60,1процентов введенной дозы выделяется через фекалии (37,5процентов) и мочу (22,6процентов). После процедуры ускоренного выведения с использованием холестирамина было выведено еще 23,1процента, в основном с фекалиями. На основании средних фармакокинетических параметров, рассчитанных на основании анализа популяционной фармакокинетики с использованием данных о пациентах с рассеянным склерозом и здоровых добровольцах период полувыведения после многократного приема дозы 14 мг составляет приблизительно 19 дней. Общий клиренс терифлуномида после однократного внутривенного введения из организма составил 30,5 мл/ч.

Процедура ускоренного выведения

Выведение препарата Абаджио из кровотока можно ускорить с помощью назначения холестирамина или активированного угля, путем прерывания процесса реабсорбции в кишечнике. Концентрации терифлуномида, измеренные во время 11-дневной процедуры, направленной на ускорение выведения терифлуномида с помощью приема:

  • холестирамина в дозе 4 г 3 раза в день;
  • холестирамина 8 г 3 раза в день;
  • 50 г активированного угля 2 раза в день;

после прекращения терапии препаратом Абаджио, указывают на то, что эти схемы привели к снижению концентрации вещества в плазме более чем на 98процентов. При этом действие холестирамина было более быстрым, чем воздействие активированного угля. Выбор между процедурами ускоренного выведения зависит от переносимости пациентом. При плохой переносимости холестирамина в дозе 8 г 3 раза в день, можно использовать дозу 4 г 3 раза в день. В качестве альтернативы можно также использовать активированный уголь.

Пропорционально дозе после перорального введения терифлуномида от 7 до 14 мг увеличивается системное воздействие.

Фармакокинетика у особых групп пациентов

Применение при нарушениях функции печени

Не требуется коррекция дозы у пациентов с печеночной недостаточностью легкой, средней или тяжелой степени.

Терифлуномид противопоказан пациентам с печеночной недостаточностью тяжелой степени.

Применение при нарушениях функции почек

Не требуется коррекция дозы у пациентов с почечной недостаточностью легкой, средней или тяжелой степени, не находящихся на гемодиализе.

В клинических исследованиях пациенты с почечной недостаточностью тяжелой степени, находящиеся на гемодиализе, не принимали участия. Терифлуномид этой группе пациентов противопоказан.

Применение у детей

Не установлена безопасность и эффективность у детей в возрасте до 18 лет. Праперат Абаджио у детей в возрасте до 10 лет для лечения рассеянного склероза не назначается.

Применение Абаджио у пожилых пациентов

Препарат Абаджиос осторожностью необходимо назначать пациентам в возрасте 65 лет и старше в связи с недостаточным количеством данных о безопасности и эффективности в данной возрастной группе.

Клиническая эффективность и безопасность Абаджио

Эффективность Абаджио была продемонстрирована в ходе исследования, которое было посвящено оценке ежедневного приема герифлуномида в дозе 7 мг и 14 мг у пациентов с рецидивирующим рассеянным склерозом (РРС). У пациентов был отмечен, как минимум, 1 рецидив в течение года, предшествующего исследованию или, как минимум, 2 рецидива за 2 года, предшествующих исследованию. При включении в исследование средний балл по расширенной шкале инвалидности (EDSS) составлял ≤ 5,5. Средний возраст популяции исследования — 37,9 лет. Большинство пациентов имели рецидивирующий ремитирующий рассеянный склероз (97,5%), но были подгруппы пациентов с вторичным прогрессирующим (0,8%) или прогрессирующе-рецидивирующим рассеянным склерозом (1,7%).

Эффективность препарата Абаджио сравнивали с эффективностью подкожной формы интерферона бета-1а (в рекомендованной дозировке, составляющей 44 мкг, три раза в неделю). Минимальная продолжительность лечения, составила 48 недель; максимальная -114 недель. Риск неэффективности терапии (подтвержденный рецидив или полное прекращение лечения) стал первичной конечной точкой. Количество пациентов, постоянно прекративших лечение, в группе терифлуномида 14 мг — 22 из 111 (19,8процентов). Причинами были нежелательные явления (10.8 процентов), недостаточная эффективность (3.6 процентов), другие причины (4,5процентов) и потеря для дальнейшего наблюдения (0,9процентов). Количество пациентов, постоянно прекративших лечение, в группе интерферона бета-1а — 30 из 104 (28.8процентов). Причинами были нежелательные явления (21,2%), недостаточная эффективность (1.9%), другие причины (4,8%) и невыполнение условий протокола (1%). Терифлуномид в дозе 14 мг/день не превосходил интерферон-бета 1а по влиянию на первичную конечную точку. Процент пациентов с подтвержденной неудачей терапии к 96-ой неделе составил 41,1% на фоне терифлуномида 14 мг по сравнению с 44,4% на фоне интерферона бета-1а.

Клинические данные о безопасности и эффективности применения терифлуномида у детей в возрасте от 0 до 18 лет отсутствуют.

Применение Абаджио во время беременности

препарат обладает тератогенным и эмбриотоксическим действием у животных, в случае использования в дозах, эквивалентных терапевтическим дозам у человека.

Фармацевтические характеристики

Пятиугольные таблетки, покрытые пленочной оболочкой. От бледно-голубого до пастельно-голубого цвета с гравировкой «14» на одной стороне таблетки и логотипом на другой.

Упаковка, срок годности, условия хранения

По 14 таблеток, покрытых пленочной оболочкой, помещают в блистер из алюминиевой фольги. По 2 блистера помещают в упаковку типа «рукав». По одной упаковке типа «рукав» вместе с инструкцией по применению помещают в пачку картонную.

Хранить препарат Абаджио необходимо при температуре не выше 30°С в защищенном от света месте. Хранить в недоступном для детей месте.

Срок годности 3 года. Не использовать по истечении срока годности.

 

 

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а также можем отправить Абаджио (Терифлуномид) по регионам Казахстана: Нур-Султан (Астана), Шымкент, Талдыкорган, Актау и другие.

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