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Имбрувика — Imbruvica (Ибрутиниб) 140 Мг

ИМБРУВИКА (IMBRUVICA) – ИБРУТИНИБ (IBRUTINIB) 140 МГ Европа

Имбрувика — Imbruvica (Ибрутиниб) 140 Мг

Компания Medical&Pharma предлагает современное лекарство Имбрувика (Ибрутиниба). Он относится к группе противоопухолевых препаратов, который содержит активное вещество Ибрутиниб,  являющийся ингибитором протеинтирозинкиназы. Лекарственное средство выпускается в форме капсул. Вещество образовывает ковалентную связь с цистеиновыми остатками, за счет чего происходит дальнейшее ингибирование ферментативной активности тирозинкиназы Брутона, а следовательно ведет к снижению активации сигнальных механизмов, необходимых для миграции В-клеток, их адгезии и хемотаксиса.

Категория:

Описание

Компания Medical&Pharma предлагает современное лекарство Имбрувика (Ибрутиниба). Он относится к группе противоопухолевых препаратов, который содержит активное вещество Ибрутиниб,  являющийся ингибитором протеинтирозинкиназы. Лекарственное средство выпускается в форме капсул. Вещество образовывает ковалентную связь с цистеиновыми остатками, за счет чего происходит дальнейшее ингибирование ферментативной активности тирозинкиназы Брутона, а следовательно ведет к снижению активации сигнальных механизмов, необходимых для миграции В-клеток, их адгезии и хемотаксиса.

Состав

одна капсула содержит:

  • действующее вещество: ибрутиниб 140 мг
  • вспомогательные вещества: целлюлоза микрокристаллическая, кроскармеллоза натрия, натрия лаурилсульфат, магния стеарат;
  • оболочка: титана диоксид, желатин;
  • чернила: Opacode S-1-17823 (глазурь фармацевтическая (шеллака раствор в этаноле), железа оксид черный, n-бутанол, 2-пропанол, аммония гидроксид 28%, пропиленгликоль);

Показания к применению

  • Мантийноклеточная лимфома (МКЛ)
  • Лечение взрослых пациентов с рецидивирующей или рефрактерной мантийноклеточной лимфомой.
  • Хронический лимфоцитарный лейкоз (ХЛЛ).
  • Лечение взрослых пациентов с хроническим лимфолейкозом:
  1. ранее не получавших терапию,
  2. которым противопоказана химиоиммунотерапия флударабином,
  3. у которых не удалось добиться ответа по крайней мере на одну линию терапии,
  4. у которых выявлена делеция 17р или мутация в гене ТР53.
  • Лечения макроглобулинемией Вальденстрема.
  • Для лиц с хронической реакцией «трансплантат против хозяина».
  • Для лиц с лимфомой маргинальной зоны и которые получили, по крайней мере, один курс анти-CD20-направленной терапии.

 

Фармакодинамика

Ибрутиниб является мощным низкомолекулярным ингибитором тирозинкиназы Брутона (ТКБ), связываясь в его активном центре с цистеиновым остатком (Cys 481), тем самым приводя к надежному ингибированию ферментативной активности тирозинкиназы Брутона. ТКБ, относящаяся к представителям семейства киназ Тес, выступает в качестве основной сигнальной молекулы цитокиновых рецепторов и антигенных рецепторов В-клеток (BCR). Сигнальный путь BCR участвует в патогенезе нескольких В-клеточных злокачественных новообразований, включая фолликулярную лимфому, лимфому из клеток мантийной зоны, В-клеточный хронический лимфоцитарный лейкоз/лимфому из малых лимфоцитов, диффузную крупноклеточную В-клеточную лимфому. Основная роль ТКБ в сигнальной активности В-клеточных рецепторов влечет к активации сигнальных механизмов, необходимых для миграции В-клеток, их адгезии и хемотаксиса. По результатам исследований ибрутиниб in vivo подавляет пролиферацию и выживаемость злокачественных В-клеток, а также in vitro ингибирует миграцию клеток и их адгезию к субстратам.

Лимфоцитоз

В начале терапии у большинства пациентов (66%) с хроническим лимфоцитарным лимфомой/лейкозом из малых лимфоцитов, принимавших монотерапию Ибрутинибом, отмечалось обратимое увеличение количества лимфоцитов (т.е. на 50% и более от исходного уровня с абсолютными значениями 5000/мкл и более), часто сопровождавшееся уменьшением лимфаденопатии. Этот эффект также наблюдался у некоторых пациентов (35%) с лимфомой из клеток мантийной зоны, получавших препарат Имбрувика. Отмечаемый лимфоцитоз — это выражение фармакодинамического эффекта, и его не следует считать прогрессированием заболевания (при отсутствии других клинических проявлений). При обоих заболеваниях лимфоцитоз как правило проявляется в течение первых месяцев лечения препаратом Имбрувика и обычно разрешается с медианой 8 и 14 недель у пациентов с хроническим лимфоцитарным лейкозом/лимфомой из малых лимфоцитов и рефрактерной или рецидивирующей лимфомой из клеток мантийной зоны.
При применении Ибрутиниба у больных с хроническим лимфоцитарным лейкозом/лимфомой из малых лимфоцитов в составе комбинированной терапии с ритуксимабом и бендамустином или с обинутузумабом лимфоцитоз отмечался редко (у 7% пациентов в группе, принимавшей терапию Ибрутинибом + ритуксимаб + бендамустин по сравнению с 6% пациентов в группе, принимавшей плацебо + бендамустин + ритуксимаб; и у 7% пациентов в группе, принимавшей препарат Имбрувика + обинутузумаб по сравнению с 1% пациентов в группе, принимавшей хлорамбуцил и обинутузумаб).
Не наблюдался лимфоцитоз у пациентов с макроглобулинемией Вальденстрема, получавших терапию Ибрутинибом.

Агрегация тромбоцитов in vitro

При in vitro исследовании ибрутиниб подавлял индуцированную коллагеном агрегацию тромбоцитов в образцах из группы лиц с нарушениями функции почек или получающих варфарин и из группы здоровых добровольцев. Количество ингибирования индуцированной коллагеном агрегации тромбоцитов в группе лиц, получающих аспирин, отмечалась реже, т.к. в такой группе индуцированная коллагеном агрегация тромбоцитов была снижена без влияния ибрутиниба. Ибрутиниб не продемонстрировал значимого ингибирования агрегации тромбоцитов, связанной с 4 агонистами аденозина фосфата (АДФ), ристоцетином, арахидоновой кислотой и тромбиновым рецептором-активатором пептида 6 (ТРАП-6) в данных группах лиц и у здоровых добровольцев.

Фармакокинетика

Всасывание

После перорального приема препарат Имбрувика быстро всасывается, при этом среднее время колеблется от 1 до 2 часов. Абсолютная биодоступность натощак (n=8) составила 2,9% (90% ДИ = 2,1-3,9), при приеме с пищей эта цифра удваивается. Фармакокинетика ибрутиниба значительно не отличается у пациентов с различными В-клеточными злокачественными образованиями. Системная экспозиция при пероральном приеме вещества повышается пропорционально дозе до 840 мг. Значение AUC, измеренное в условиях равновесного состояния (среднее ± стандартное отклонение), составило 953 ± 705 нг*ч/мл для дозы 560 мг и 680 ± 517 нг*ч/мл для дозы 420 мг. При приеме препарат Имбрувика натощак отмечается повышение системной экспозиции на 60% по сравнению с приемом через 30 минут после еды, за 30 минут до еды или через 2 часа после завтрака с высоким содержанием жиров.

Распределение

in vitro обратимое связывание ибрутиниба с белками плазмы составило 97.3%, при этом в диапазоне концентрации от 50 до 1000 нг/мл зависимость от концентрации отсутствовала. Объем распределения составлял 683 л, а кажущийся объем распределения в равновесном состоянии составил около 10000 л.

Метаболизм

Метаболизируется препарат главным образом изоформой CYP3A4/5 цитохрома Р450 с образованием дигидродиольного метаболита, подавляющая активность которого в отношении ТКБ примерно в 15 раз ниже, чем у ибрутиниба. Системная Css дигидродиольного метаболита сопоставима с таковой исходного препарата.
По данным исследований in vitro участие изофермента CYP2D6 в окислительном метаболизме ибрутиниба составляет менее 2%. Кроме этого, по результатам исследования баланса масс у человека фармакокинетический профиль у пациентов со слабой и высокой активностью изофермента CYP2D6 (по данным генотипирования) был одинаков. Таким образом, у пациентов с различными генотипами изофермента CYP2D6 не требуются меры предосторожности.

Выведение

При приеме натощак венозный клиренс составил 62 л/час, а в сочетании с пищей — 72 л/час. В связи с прявленным эффектом «первого прохождения» кажущийся клиренс после перорального приема составил 2000 л/час при применении натощак и 1000 л/час при применении с пищей. Период полувыведения ибрутиниба составляет 4-6 часов.
После однократного перорального приема радиоактивного меченого [14С]-ибрутиниба здоровыми добровольцами приблизительно 90% радиоактивности было выведено в течение 168 часов. Большая часть (80%) выводилась с фекалиями, менее 10% выводилось с мочой. Неизменённый ибрутиниб составлял около 1% радиоактивного меченого продукта в фекалиях и не обнаруживался в моче. Остальные продукты экскреции представляли собой метаболиты.

Фармакокинетика у особых групп пациентов

Пожилые пациенты

Было показано, по данным популяционных фармакокинетических исследований, что возраст не оказывает значимого влияния на клиренс ибрутиниба из крови.
Пациенты с почечной недостаточностью
Экскреция ибрутиниба почками минимальна. Экскреция метаболитов с мочой составляет менее 10%. Но в то же время, не проводилось отдельных клинических исследований ибрутиниба у больных с различными нарушениями функции почек. У лиц с легкой и умеренной степенью нарушений функций почек (клиренс креатинина более 30 мл/мин) не требуется коррекция дозы. Отсутствуют данные о лицах с тяжелой почечной недостаточностью либо находящихся на диализе.

Дети и подростки (от 18 лет и младше).

Не проводились исследования фармакокинетики препарата Имбрувика у пациентов в возрасте до 18 лет.

Пациенты с нарушением функции печени.

Ибрутиниб метаболизируется в печени. Было проведено исследование у пациентов с нарушением функции печени без злокачественных образований, принимавших Ибрутиниб натощак в дозе 140 мг. AUClast ибрутиниба увеличивалась в 2.7, 8.2 и 9.8 раза у пациентов с нарушением функции печени: легкой (n=6, класс А по шкале Чайлд-Пью), средней (n=10, класс B по шкале Чайлд-Пью) и тяжелой (n=8, класс C по шкале Чайлд-Пью).
Концентрация свободной части ибрутиниба также повышается при увеличении степени нарушения функции печени составляет 3.0%, 3.8% и 4.8% у лиц с нарушением функции печени легкой, средней и тяжелой степени соответственно. У здоровых добровольцев свободная фракция составляет 3.3%. Концентрация несвязанного ибрутиниба (AUCunbound,last) увеличивается примерно в 4.1, 9.8 и 13 раз у лиц с нарушением функции печени легкой, средней и тяжелой степени соответственно.

Доклинические данные

В доклинических исследованиях продолжительностью в проведенных на крысах и собаках до 13 недель регистрировались следующие нежелательные явления. Пррепарат в человеческих эквивалентных дозах (ЭД) у крыс ≥16 мг/кг/день и у собак ≥32 мг/кг/день приводил к нарушениям со стороны желудочно-кишечного тракта (воспалительные процессы и/или жидкий стул/диарею). Также была отмечена дисфункция лимфатической системы (лимфоидное истощение), у крыс, принимавших ЭД ≥28 мг/кг/день, и у собак, принимавших ЭД ≥32 мг/кг/день. При повышении ЭД у крыс до ≥6 мг/кг/день отмечалась атрофия ацинарных клеток поджелудочной железы. К тому же, у крыс, принимавших ЭД ≥16 мг/кг/день в течение 13 недель, наблюдалось снижение трабекулярной и кортикальной костной массы. Все эти признаки почти полностью или частично исчезали после 6-13 недель восстановления.

Мутагенность/канцерогенность

Канцерогенность ибрутиниба не исследовалась. В исследованиях на бактериях, клетках мышей и млекопитающих генотоксичных свойств не выявлено.

Репродуктивная токсичность

Исследовали на беременных крысах влияние вещества на развитие эмбриона и плода при пероральном введении в дозе 10, 40 и 80 мг/кг/день. При приеме ибрутиниба в дозе 80 мг/кг/день (приблизительно 14-кратное превышение AUC для ибрутиниба и 9,5-кратное увеличение AUC дигидродиольного метаболита в сравнении с человеческой дозой 560 мг в сутки) отмечалось повышение количества выкидышей и количества висцеральных пороков (крупных сосудов и сердца).
Применение ибрутиниба в дозе 40 мг/кг/день (приблизительно 5,6-кратное превышение AUC ибрутиниба и 4,0-кратное превышение AUC дигидродиольного метаболита по сравнению с человеческой дозой 560 мг в сутки) вызывало снижение массы плода. К тому же, применялся ибрутиниб и у беременных крольчих в дозе 5,15 и 45 мг/кг/день в фазу органогенеза. Применение в дозе 15 мг/кг/день и выше влекло за собой развитие скелетных аномалий (аномалии грудной клетки).
При использовании ибрутиниба в дозе 45 мг/кг/день наблюдалось увеличение количества выкидышей. При использовании ибрутиниба в дозе 15 мг/кг/день (что эквивалентно AUC у лиц с МКЛ, принимающих по 560 мг/день, или в 2,8 раза выше, чем у пациентов с ХЛЛ и БВ, принимающих 420 мг/день) у новорожденных кроликов отмечались пороки развития.

Фертильность

Не наблюдалось каких-либо нарушений фертильности и репродуктивной функции у самцов и самок крыс при приеме вещества до максимальной дозы 100 мг/кг/день.

Фармацевтические характеристики

Желатиновые капсулы, содержащие — порошок белого или почти белого цвета.

Упаковка, срок годности,

условия хранения

Капсулы Имбрувика, твердые желатиновые, упакованные в пластиковую тару, корпус и крышечка белого цвета, с надписью «ibr 140 mg» на крышке.
Упакованы по 90, 120 капсул. Хранить в защищенном от света недоступном для детей месте, при температуре не выше 25°С.

 

 

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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Позвоните и узнайте цену Имбрувика (Ибрутиниб)

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

 

Детали

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Великобритания

Тип

Капсулы

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    Clients recognize the natural and clear elements of the nutritional complement.
    They worth the combination of amino acids and
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    can give you the results. Creatine and BCAAs can enhance muscle building and performance-related objectives, however sleep, food
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    The product is made with pure caffeine you could modify based on your needs.
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    Citrulline malate is a compound made up of the amino
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    be sure that the speed of muscle protein synthesis is bigger than muscle protein catabolism
    over a long period of time. In reality, it’s inspired if your goal is
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    Relying on your objectives and individual preferences, you would possibly contemplate including different supplements to the combo.
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    for restoration. BCAAs are often used to support muscle restoration and scale back muscle soreness after train.
    Prospects respect the energizing impact of this nutritional
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    Caffeine is likely considered one of the most researched and efficient performance enhancers ever.
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    More ATP means more reps, extra weight, and more muscle progress over time.
    Recovery is necessary for exercise and, with out permitting
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    that can hamper your course of (6). Lowered recovery occasions from creatine supplements additionally help you to push
    your self further and more regularly. Earlier Than you start taking
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    Yes, creatine is great for enhancing your workouts, but it’s also useful for accelerated muscle restore.

    The norm is for pre-workout dietary supplements to include a complete lot of caffeine, usually ranging
    from 150 mg to 350 mg in a serving. Kaged has supplied us with the best high quality,
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    One scoop is more than enough to have you destroying your workouts, but
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    Plus, you’re getting 30 servings in each tub, which many manufacturers don’t do anymore.

    Whereas few research are trying at the impact of mixing BCAAs and creatine,
    there are several out there that take a look at the efficacy of performance blends containing each creatine and BCAAs.
    Based on available research, there’s nothing to point that mixing BCAAs
    and creatine is unsafe or will cause adverse results.
    Creatine’s also one of the most well-liked and extensively used ergogenic aids because
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    They can assess your dietary habits, fitness objectives, and potential deficiencies to advocate probably the most suitable supplements and dosages.
    Beta-alanine is thought for its capacity to increase muscle carnosine
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    Pay consideration to how your body responds to the combination of creatine, BCAAs, and glutamine.

    BETA-ALANINEBeta-alanine has been a very popular ingredient for
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    Creatine supports ATP manufacturing, which helps to replenish cellular
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    She also appreciates that everything is listed instantly on the label.

    «100% clear components mean no proprietary blends, so you realize precisely what you’re putting into your physique,» says Werner.
    For these trying to maximize performance and optimize strength, output, focus and restoration, this pre-workout may be value a attempt, according to Werner.
    She explains that it incorporates naturally-derived ingredients and is NSF Certified
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    it incorporates Peak ATP, an artificial type of ATP,
    which is used for power production within the body.
    BCAAs are also usually used as a post-workout recovery aid, as they might help to stimulate muscle protein synthesis and promote the repair and progress of muscle tissue.
    While most studies suggest that BCAAs are unlikely to enhance train efficiency or muscle
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    Creatine presents the benefit of increased energy output and enhanced performance in high-intensity workout routines, whereas BCAAs assist mitigate exercise-induced muscle
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    lean physique. Usually, those who would profit most from using BCAAs, creatine, and pre-workout are
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    This contains athletes coaching for competitions or intense workouts and individuals aiming to
    extend muscle mass or energy. Combining BCAAs with creatine and pre-workout
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    This abdomen sensitivity problem is why I
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    get the job carried out. When we’re speaking bout BCAAs,
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    But, doing so decreases concentrations of the opposite two amino acids, which
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    BCAAs will be helpful if you’re in search of an alternative gasoline supply to carbohydrates earlier than or during your workout.
    And BCAAs will be helpful if you’re looking to cut back
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    exercise program. The product contains solely caffeine and amino acids, with no fillers.
    It’s onerous to know where to begin in terms of workout supplements.

    They all sound helpful in terms of constructing muscle, however you
    might be interested in which dietary supplements you can (and should) take collectively and which ones will help you achieve your particular objectives.
    Here, we’ll speak about what Branched Chain Amino Acids (BCAA) and creatine can do for
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    Caffeine, for instance, could trigger signs like decreased
    vitality, drowsiness and decreased alertness as the stimulant wears off.

    «A pre-workout shouldn’t be taken in place of a health-promoting and performance-supporting food regimen,»
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    give you the outcomes you want. While many pre-workout formulations
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    It’s additionally important for customers to keep a tally of their general ingestion of sure ingredients corresponding to caffeine and niacin,
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    Altius is a clinically-dosed, «No BS» pre exercise with none synthetic sweeteners or unnecessary filler elements.

    Next on the record is one of the best excessive caffeine pre-workout with creatine!

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    All The Time search the recommendation of your
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    So I truly have it in your post-workout as properly to replenish those ranges.
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    Pairing your creatine and protein powder in a protein shake
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    Customers find that the product works nicely for getting them
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    They say it tastes good, works properly, and is a dependable complement that provides unbelievable
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    «Creatine supplementation is protected throughout short- and long-term use for healthy men and women and in younger and older individuals,» says Balls.
    And it could possibly profit a variety of individuals, from pro athletes to recreational
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    People who’re fasting (for health, spiritual, or other
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