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Нинларо — Ninlaro (иксазомиб)

Нинларо (иксазомиб)

Нинларо — Ninlaro (иксазомиб)

Препарат Нинларо (иксазомиб) − первый и единственный пероральный ингибитор протеасом для лечения пациентов с рецидивирующей и/или резистентной множественной миеломы, использующийся в комбинации с леналидомидом и дексаметазоном. Нинларо – выпускается в виде капсул для приема внутрь один раз в неделю.
Действующее вещество Нинларо — Иксазомиб является селективным и обратимым ингибитором протеасомы, обладающим высокой противоопухолевой активностью и прекрасным профилем безопасности.

Категория:

Описание

Препарат Нинларо (иксазомиб) − первый и единственный пероральный ингибитор протеасом для лечения пациентов с рецидивирующей и/или резистентной множественной миеломы, использующийся в комбинации с леналидомидом и дексаметазоном. Нинларо – выпускается в виде капсул для приема внутрь один раз в неделю.
Действующее вещество Нинларо — Иксазомиб является селективным и обратимым ингибитором протеасомы, обладающим высокой противоопухолевой активностью и прекрасным профилем безопасности.

Состав

  • активное вещество: иксазомиба цитрат: 3,29/4,3/5,7 мг, что соответствует иксазомибу — 2,3/3/4 мг;
  • вспомогательные вещества: МКЦ; тальк; магния стеарат;
  • оболочка капсулы, дозировка 2,3 мг: желатин; титана диоксид; краситель железа оксид красный; чернила черные 10А21;
  • оболочка капсулы, дозировка 3 мг: желатин; титана диоксид; краситель железа оксид черный; чернила черные 10А21;
  • оболочка капсулы, дозировка 4 мг: желатин; титана диоксид; краситель железа оксид красный; краситель железа оксид желтый; чернила черные 10А21;
  • чернила черные 10А2 содержат: шеллак, калия гидроксид, пропиленгликоль, краситель железа оксид черный.

Фармакодинамика

Иксазомиб является обратимым ингибитором протеасом. Иксазомиб в основном взаимодействует и подавляет химотрипсиноподобную деятельность субъединицы бета-5 20S протеасомы.
Нинларо индуцирует апоптоз у культивируемых клеточных линий множественной миеломы in vitro. In vitro нинларо демонстрировал цитотоксичность в отношении клеток миеломы, взятых у больных с развившимися рецидивами после многократных циклов терапии, включавших бортезомиб, дексаметазон и леналидомид. Комбинация нинларо и леналидомида демонстрировала синергическое цитотоксическое действие на клеточные линии множественной миеломы. В условиях in vivo нинларо демонстрировал противоопухолевое воздействие на модели опухолевого ксенотрансплантата множественной миеломы мышей.

Кардиоэлектрофизиология

Иксазомиб не удлинял интервал QTc при воздействиях, соответствующих клиническим, по результатам фармакокинетическо-фармакодинамического анализа данных 245 пациентов.

Фармакокинетика

Всасывание

После приема внутрь медиана времени достижения максимальной концентрации нинларо в плазме была равна одному часу. Значение абсолютной биодоступности после перорального приема составляло 58% по результатам популяционного анализа фармакокинетики.
Кривая AUC нинларо повышается дозозависимым способом в диапазоне доз от 0,2 до 10,6 мг. По данным исследований влияния приема пищи, проведенное у больных, получавших однократную дозу 4 мг нинларо, показало, что пища с высоким содержанием жиров понижала AUC иксазомиба на 28% и максимальную концентрацию на 69%.

Распределение

Связывание нинларо с белками плазмы составляет 99%, распределяется в эритроциты, происходит с соотношением «кровь-плазма». Объем распределения в равновесном состоянии составляет 543 литров.

Метаболизм

После перорального приема дозы с радиоизотопной меткой иксазомиб представлял 70% всего связанного с препаратом радиоактивного материала в плазме. Основным механизмом выведения препарата нинларо считают метаболизм под действием множественных ферментов CYP и не-CYP белков. Эксперименты in vitro с применением изоферментов цитохрома Р450, произведенных на основе человеческой комплементарной ДНК, показали, что при клинически значимых уровнях концентрации иксазомиба не существует специфического изофермента CYP, главным образом участвующего в метаболизме иксазомиба. При более высоких концентрациях, чем клинические, иксазомиб подвергался метаболизму под действием многих изоформ CYP.

Выведение

По результатам фармакокинетического популяционного анализа клиренс составлял около 1,9 л/час с изменчивостью индивидуальных значений величиной 44%. Период полувыведения иксазомиба в конечной фазе составлял 9,5 суток. При пероральном еженедельном использовании отношение кумуляции было определено как двукратное.

При пероральном приеме однократной дозы меченого 14С-иксазомиба у 5 больных с распространенной злокачественной опухолью 62% поступившей радиоактивности было выведено с мочой и 22% с калом. Неизменный препарат, выведенный с мочой, составлял <3.5% введенной дозы.

Особые группы пациентов

Возраст, пол, этническая принадлежность. Не наблюдалось клинически значимого влияния возраста (в диапазоне 23-91 года), расовой принадлежности, пола или площади поверхности тела (диапазон 1,2-2,7 кв.м.) на клиренс нинларо на основании фармакокинетического популяционного анализа.

Нарушения функции печени.

Фармакокинетика иксазомиба у пациентов с нормальной функцией печени была сходной с таковой у пациентов с нарушениями функции печени легкой степени (общий билирубин ≤ВГН и АСТ>ВГН, или общий билирубин >1-1.5×ВГН и любое значение АСТ) на основании популяционного анализа фармакокинетики.

Фармакокинетические данные были описаны у пациентов с нормальной функцией печени при приеме иксазомиба в дозе 4 мг (n=12), с умеренными нарушениями функции печени при дозе 2.3 мг (общий билирубин >1.5-3×ВГН, n=13) или тяжелыми нарушениями функции печени при дозе 1.5 мг (общий билирубин > 3 × ВГН, n=18). Нормализованные по дозе средние значения AUC были на 20% выше у пациентов с умеренными или тяжелыми нарушениями функции печени по сравнению с пациентами с нормальной функцией печени.

Нарушения функции почек.

Фармакокинетика иксазомиба у пациентов с нормальной функцией почек была сходной с таковой у пациентов с нарушениями функции почек легкой или умеренной степени тяжести (КК ≥ 30 мл/мин) на основании фармакокинетического популяционного анализа.

Фармакокинетические данные были описаны при дозе иксазомиба 3 мг у пациентов с нормальной функцией почек (КК ≥ 90 мл/мин, n=18), тяжелыми нарушениями функции почек (КК < 30 мл/мин, n=14) или с заболеваниями почек в терминальной стадии, требующими диализа (n=6). Средние значения AUC были на 39% выше у пациентов с тяжелыми нарушениями функции почек или с заболеваниями почек в терминальной стадии, требующими диализа, по сравнению с пациентами с нормальной функцией почек. Нинларо не выводится при проведении диализа, о чем свидетельствует, то что концентрации препарата перед диализом, во время его проведения и после проведения диализа были сходными.

Показания препарата

  • в комбинации с дексаметазоном и леналидомидом применяется для лечения больных с множественной миеломой, получивших ранее как минимум одну линию терапии.

Описание лекарственной формы

  • Капсулы, 2,3 мг: твердые, желатиновые, № 4. Корпус и крышечка капсулы — светло-розового цвета, имеется надпись, нанесенная черными чернилами «Takeda» — на крышечке «2.3 mg» — на корпусе.
  • Капсулы, 3 мг: твердые, желатиновые, № 4. Корпус и крышечка капсулы — светло-серого цвета, имеется надпись, нанесенная черными чернилами «Takeda» — на крышечке и «3 mg» — на корпусе.
  • Капсулы, 4 мг: твердые, желатиновые, № 3. Корпус и крышечка капсулы — светло-оранжевого цвета, имеется надпись, нанесенная черными чернилами «Takeda» — на крышечке и «4 mg» — на корпусе.

Фармацевтические характеристики

Содержимое капсул — порошок от белого до желтовато-белого цвета.

Упаковка, срок годности, условия хранения

По 1 капсуле в ПВХ Алюминий/Алюминий блистер. Блистер герметично вклеен в картонную обложку и неотделим от нее. По одной картонной обложке вместе с инструкцией по применению помещают в пачку картонную. Три картонные пачки помещают в общую картонную пачку. На защитной наклейке голографическим способом указывают логотип «Takeda».

Срок годности — 3 года.

Хранить при температуре не выше 30°С. Не замораживать. Хранить в оригинальной упаковке непосредственно до приема каждой капсулы. Хранить в недоступном для детей месте.

 

 

 

Наша компания работает как на территории Казахстана, так и осуществляет доставку в страны ближнего зарубежья. Обращайтесь к нам за консультациями по контактным телефонам.

Заказать и купить Нинларо (иксазомиб) в Алматы

Заказать и купить Нинларо (иксазомиб) в Казахстане

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

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    Adjusting your Anavar dosage is a process that requires cautious monitoring of your body’s reactions.

    It’s about striking a balance between reaching desired bodily
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    Anavar might help in your bodybuilding journey,
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    and ensure any changes to your dosage are thoughtfully thought of.
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    understanding the appropriate dosage is important, and it could
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    As far as men are involved, the optimum dosage is inside the range of 15-20mg/day of Anavar with
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    going that will assist you practice with higher intensity and
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    do so alone. You nonetheless need prepare appropriately, eat
    proper and you additionally need to cycle on and
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    If (you, as a women) have expertise of taking Anavar earlier than then you might begin your cycle with
    10 mg a day and lengthen your cycle to as a lot as 6 weeks.
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    The woman in the image above (anonymous) is understood to have consumed
    10 mg of Anavar per day for aa 5-week cycle and shed appears to have lost plenty of physique
    fat which is evident from her midsection. She is thought to have increased her body weight
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    For those looking for Anavar results without coaching, let me mention it very clearly that this compound will work solely when you combine it with coaching
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    Anavar to supply outcomes. Anavar is an anabolic steroid that was created way back
    in 1962 and is also recognized as Oxandrolone.

    References:

    illegal anabolic steroids before and after (Marietta)

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    in girls. This may not sound like an issue, nevertheless, ladies can report significantly much less
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    influence self-worth, which is why burning
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    Usually, Anavar has a relatively brief half-life of round 9 to 10 hours.

    Approximately a decade after Anavar got here in the
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    cholesterol. This was due to medical doctors in the ’70s observing decreased whole
    levels of cholesterol in Anavar users (15). Our expertise and clinical research point out that elevated liver enzymes commonly return to normal following cycle
    cessation (11). Anavar is a C17-alpha-alkylated oral steroid, meaning the compound will be fully active after bypassing the liver.
    However, not like different oral steroids, Anavar is not considerably hepatotoxic.
    This is as a result of the kidneys, and never the liver, are primarily answerable for metabolizing Anavar.
    Nonetheless, we discover this to be a smaller share in comparability with different C17-aa steroids.

    But one should be cautious when doing so as a result of this could contribute to the hormonal balance that Anavar already causes.
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    Power is amongst the major components of profitable athleticism because it translates into pace and energy.

    Athletes also appreciate Anavar as a end result of the fact that it won’t produce a big buildup in mass.

    This creates a big and tight look quite than a giant, bloated mess
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    These authorized steroids take longer to work, but within a couple of months, you want to
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    Oxandrolone is a wonderful addition to a chopping and
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    Wait 14 days publish cycle to start recovery and use 50mg/day Clomid for 20 days and 0.5mg/day Arimidex alongside it.
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    Enhanced recovery enables an athlete to extend training intensity,
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    Anavar and all anabolic steroids are essentially
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    Anavar, also known as Oxandrolone, is a popular anabolic steroid that is extensively used by bodybuilders, athletes,
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    Anavar, also referred to as Oxandrolone, is an anabolic steroid used to promote muscle development, improve energy,
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    Its generic name is oxandrolone, and it was originally developed to
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    This is taken into account to be a really excessive dose for females, and it’s most
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    This will give you a recommended every day caloric consumption; when using
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    In the top, taking care of your reproductive health whereas using Anavar and contraception needs cautious thought and planning.
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    References:

    Side Effects Of Illegal Steroids (Hirefoodies.Com)

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    Furthermore, Anavar is known to have very low toxicity when used correctly;
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