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Флудара — Fludara (флударабин)

Флудара — Fludara (флударабин)

Противоопухолевый препарат, антиметаболит. Препарат Флудара представляет собой фторированный нуклеотидный аналог противовирусного средства видарабина, 9-β-D-арабинофуранозиладенина (ара-А), который относительно резистентен к дезаминированию аденозиндезаминазой.

Исследования in vitro показали, что воздействие 2-фтор-ара-А на лимфоциты больных с хроническим лимфолейкозом (ХЛЛ) активирует механизм интенсивной фрагментации ДНК и апоптоза.

Описание

Противоопухолевый препарат, антиметаболит. Препарат Флудара представляет собой фторированный нуклеотидный аналог противовирусного средства видарабина, 9-β-D-арабинофуранозиладенина (ара-А), который относительно резистентен к дезаминированию аденозиндезаминазой.

Исследования in vitro показали, что воздействие 2-фтор-ара-А на лимфоциты больных с хроническим лимфолейкозом (ХЛЛ) активирует механизм интенсивной фрагментации ДНК и апоптоза.

Токсичен. Обладает тератогенной активностью. Мутагенными свойствами не обладает.

Состав Флудара

  •  Активное вещество: флударабина фосфат 10,000 мг;
  •  дополнительные вещества: целлюлоза микрокристаллическая, лактозы моногидрат, кармеллоза натрия (натрия карбоксиметилцеллюлоза), кремния, магния стеарат, диоксид коллоидный;
  • оболочка таблетки: гипромеллоза (гидроксипропилметилцеллюлоза 2910), тальк, титана диоксид, железа (II) оксид, железа (III) оксид.

Фармакодинамика препарата Флудара

Противоопухолевый препарат, антиметаболит. Препарат представляет собой фторированный нуклеотидный аналог противовирусного средства видарабина, 9-β-D-арабинофуранозиладенина (ара-А), который относительно резистентен к дезаминированию аденозиндезаминазой.

В организме пациента флударабина фосфат быстро дефосфорилируется до 2-фтор-ара-А. Данный метаболизм который, захватываясь клетками, затем внутриклеточно фосфорилируется до активного трифосфата (2-фтор-ара-АТФ). Данный метаболит ингибирует РНК-редуктазу, ДНК-полимеразу (альфа, дельта и ипсилон), ДНК-праймазу и ДНК-лигазу, что приводит к нарушению синтеза ДНК у мишени. Кроме того, частично угнетается РНК-полимераза II с последующим понижением белкового синтеза.

Препарат Флудара содержит флударабина фосфат — это фторированный нуклеотидный аналог противовирусного агента видарабина, 9-β-D-арабинофуранозиладенина (ара-А), который относительно резистентен к дезаминированию аденозиндезаминазой.

Исследования in vitro показали, что воздействие 2-фтор-ара-А на лимфоциты больных с хроническим лимфолейкозом (ХЛЛ) активирует механизм интенсивной фрагментации ДНК и апоптоза.

Токсичен. Обладает тератогенной активностью. Мутагенными свойствами не обладает.

Фармакокинетика Флудара

Четкой корреляции между фармакокинетикой флударабина и его лечебным результатом у онкологических больных не выявлено, при этом частота обнаружения нейтропении и изменения гематокрита является дозозависимой.

Распределение и метаболизм

Флударабина фосфат (2-фтор-ара-АМФ) является водорастворимым предшественником флударабина (2-фтор-ара-А), в организме пациента 2-фтор-ара-АМФ быстро и полностью подвергается дефосфорилированию до нуклеозида 2-фтор-ара-А.

Связывание с белками плазмы крови незначительное.

2-фтор-ара-А активно транспортируется в лейкемические клетки, после рефосфорилируется до монофосфата и частично до ди- и трифосфата. Трифосфат (2-фтор-ара-АТФ) является основным внутриклеточным метаболитом и единственным из известных метаболитов, обладающих цитотоксической активностью. Концентрация 2-фтор-ара-АТФ в лейкемических клетках была значительно выше, чем его максимальная концентрация в плазме, что указывает на накопление вещества в опухолевых клетках.

Период полувыведения (T1/2) 2-фтор-ара-АТФ из клеток-мишеней составляет в среднем от 15 до 23 часов.

Выведение Флудара

2-фтор-ара-А выводится преимущественно почками (от 40 процентов до 60 поцентов введенной в/в дозы).

Фармакокинетика

Четкой корреляции между фармакокинетикой флударабина и его лечебным результатом у онкологических больных не выявлено, при этом частота обнаружения нейтропении и изменения гематокрита является дозозависимой. Флударабина фосфат (2-фтор-ара-АМФ) является водорастворимым предшественником флударабина (2-фтор-ара-А). В организме человека 2-фтор- ара-АМФ быстро и полностью подвергается дефосфорилированию до нуклеозида 2-фтор-ара-А. Связывание с белками плазмы крови незначительное.

2-фтор-ара-А выводится преимущественно почками.

После приема внутрь максимальная концентрация (Сmах) (20-30 процентов от концентрации, определяемой к концу внутривенной системы) в крови наблюдается через 1-2 часа. Биодоступность составляет 50-65процентов. Пища незначительно (менее 10 процентов) увеличивает площадь под кривой концентрация-время (AUC) и снижает Тmах (время достижения максимальной концентрации) и Сmах (максимальной концентрации), не изменяет период полувыведения.

При хронической почечной недостаточности клиренс флударабина снижается.

Показания к применению  препарата Флудара

  • В-клеточный хронический лимфолейкоз (в качестве терапии первой линии);
  • Терапия препаратом в качестве терапии первой линии может быть начата только у больных с прогрессирующим заболеванием, либо на стадиях A/В
  • В-клеточный хронический лимфолейкоз (у больных , которые резистентны к терапии алкилирующими препаратами, или у которых наблюдается прогрессирование заболевания во время или после использования, как минимум, одной стандартной схемы лечения, содержащей алкилирующие препараты;
  •  неходжкинские лимфомы низкой степени злокачественности;
  •  фолликулярные В-клеточные лимфомы;
  •  лимфомы из клеток мантийной зоны.

Применение при беременности и детям

Беременность

Применение препарата противопоказано во время беременности. Пациентки детородного возраста должны избегать зачатия и применять надежные методы контрацепции во время лечения и не менее 6 месяцев после окончания лечения препаратом Флударa.

Период грудного вскармливания

Во время терапии препаратом не следует начинать грудное вскармливание. При необходимости использования препарата Флудара, пациентки, кормящие грудью, должны прекратить грудное вскармливание.

Дети

Не рекомендуется применять препарат у детей в возрасте младше 18 лет, так как данных по эффективности и безопасности его применения у данной категории пациентов недостаточно.

Пожилые пациенты

Так как имеются ограниченные данные по использованию препарата Флудара у пациентов пожилого возраста (старше 75 лет), то у данной категории пациентов препарат следует применять с осторожностью. У пациентов в возрасте 65 лет и старше, необходимо контролировать клиренс креатинина до начала лечения.

Пациенты с нарушением функции почек

У пациентов со снижением функции почек необходима коррекция дозы. При клиренсе креатинина от 30 до 70 мл/мин необходимо уменьшить дозу на 50 процентов и проводить тщательный гематологический контроль для оценки. Имеются ограниченные клинические данные об использовании препарата для лечения пациентов с нарушением функции почек (клиренс креатинина <70 мл/мин). У пациентов с почечной недостаточностью препарат должен применяться с осторожностью . При клиренсе креатинина <30 мл/мин применение препарата Флудара противопоказано.

Пациенты с нарушением функции печени

У пациентов с нарушением функции печени безопасность и эффективность использования препарата не изучены. Следует соблюдать осторожность при применении флударабина у пациентов.

Особые указания

Препарат Флудара следует вводить только внутривенно.

При лечении препаратом Флудара рекомендуется периодически оценивать показатели периферической крови, для профилактики выявления анемии, тромбоцитопении и нейтропении, тщательно контролировать концентрацию креатинина в сыворотке крови и КК, а также осуществлять тщательный мониторинг за функцией ЦНС с целью своевременного выявления возможных неврологических расстройств.

Угнетение костного мозга обычно носит обратимый характер. При лечении препаратом Флудара солидных опухолей у взрослых наибольшее снижение числа нейтрофилов в среднем наблюдается на 13-й день (3-25 день) от начала терапии, тромбоцитов — в среднем на 16-й день (2-32 день). Миелосупрессия может быть выраженной и иметь кумулятивный характер. Продолжительность клинически значимой панцитопении составляла от 2 месяцев до 1 года.

Эффекты длительного применения препарата Флудара на ЦНС неизвестны.

На фоне лечения препаратом Флудара было отмечено развитие серьезных оппортунистических инфекций, в некоторых случаях приводящих к смерти. Больным с повышенным риском развития оппортунистических инфекций рекомендовано проведение профилактической терапии.

После провокационной пробы с препаратом у большинства пациентов с гемолитической анемией отмечался рецидив гемолиза. Пациенты, принимающие лечение препаратом , должны тщательно наблюдаться на предмет выявления признаков гемолитической анемии. В случае развития гемолиза рекомендуется прекращение терапии препаратом Флудара. Наиболее распространенными лечебными мероприятиями при гемолитической анемии являются трансфузии облученной крови и терапия ГКС.

Ввиду того, что препарат может вызывать лизис опухоли уже на первой неделе терапии, следует соблюдать осторожность при лечении пациентов с риском развития этого синдрома (особенно при большой опухолевой массе). Следует иметь в виду, что пациенты, устойчивы к терапии препаратом Флудара, в большинстве случаев проявляют устойчивость и к хлорамбуцилу.

Следует избегать вакцинации живыми вакцинами во время и после лечения препаратом Флудара .

Влияние на способность к управлению транспортными средствами и механизмами

Некоторые побочные реакции препарата Флудара, такие как повышенная усталость, нарушения зрения, слабость могут отрицательно влиять на способность к вождению автомобиля и выполнению потенциально опасных видов деятельности, требующих повышенной концентрации внимания и быстроты психомоторных реакций.

Применение при беременности и кормлении грудью

Препарат Флудара противопоказан к использованию при беременности и в период лактации (грудного вскармливания).

Женщины и мужчины детородного возраста должны использовать надежные методы контрацепции во время и не менее 6 месяцев после окончания терапии.

Упаковка, срок годности, условия хранения Флудара

По 20 таблеток в каждой упаковке. Условия хранения препарата Флудара при температуре не выше 30 °C. Хранить в недоступном для детей месте.

Срок годности препарата Флудара

  • лиофилизат для приготовления раствора для внутривенного вливания 50 мг — 3 года.
  • восстановленный раствор надо использовать не позднее 8 ч после приготовления.
  • таблетки, покрытые пленочной оболочкой 10 мг — 3 года.

Не применять по истечении срока годности, указанного на упаковке.

 

 

 

 

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

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    Specialists often debate the effectiveness of varied training splits.

    Many agree that the most effective break up largely depends on individual goals and circumstances.
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    For occasion, should you miss a workout, you presumably can simply shift your schedule somewhat than really feel
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    This superior energy and muscle constructing program is designed to burst the sleeves
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    Shredding body fats and getting lean, is really about coaching intensity and
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    It turned out that only the group that skilled with very light weights skilled sub-optimal muscle development – within the
    other three groups, muscle progress was comparable. The lightest
    group used 20% of their 1RM (max), which they lifted for about 50–85 reps per set.

    Mass marked exercises are people who assist you to build crude
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    In distinction our exercise plan allows you to activate protein synthesis twice in the week, creating a more favorable surroundings for muscle development to freely occur.

    Now do one other 6 partial reps, pause for three seconds within the
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    First up after the bench press is the incline dumbbell press,
    for three units of 8 reps. The incline dumbbell presses complement the bench press by targeting the upper
    portion of your chest more. Moreover, the
    dumbbells will help you uncover and correct any side-to-side asymmetries you may need.
    The bench press is at the same time elegantly easy and ruthlessly efficient for
    growing your chest dimension and strength. Load up the bar, press it for reps,
    and repeat frequently – each time attempting to add a little
    little bit of weight to the bar, or another rep to your set.
    Nevertheless, this training these muscular tissues together
    is environment friendly and efficient.
    It could be the same split with modifications to the workouts
    and structure or it can be a totally totally different cut up.
    Avoid doing pushing muscle teams and pulling muscle teams back to
    again. For instance, you don’t want to do Chest on Day 1 after
    which Shoulders on Day 2.
    If you need a chiseled 6-pack, you have to develop
    your again and oblique core muscle tissue as nicely. In Any Other Case,
    your athletic and everyday efficiency will suffer and you’ll be significantly more susceptible to accidents.
    Fortunately, many of those workout routines may be carried out with bodyweight only
    and don’t require fancy tools or a gym membership.

    If you’re using a machine, sit down and put the pad
    down so that your legs are secured. In many circumstances, when first starting out,
    it could be greatest to easily purpose for a few muscle groups every day
    and give consideration to a quantity of easy workout routines that concentrate on them.

    For this purpose, some people may prefer to do quad-dominant leg
    workout routines in the future and hamstring/glute dominant
    exercises on another. That’s a good option if your leg growth is lagging behind the rest of your body and needs some additional consideration. Your workout should match your coaching objective, the amount
    of time you need to practice, your expertise, and your current level of health and
    power. Unnecessary to say, a cookie-cutter program is not going to match these criteria.

    For intermediate to advanced lifters, the PPL or basic bodybuilder cut up might be
    best for muscle acquire. These routines permit more quantity (exercises &
    sets) to the muscle teams in a given exercise,
    which is likely needed to adequately break down and stimulate the muscle tissue of a seasoned lifter.
    After a coaching cycle, you will take a week break
    or a deload interval. Once you start the next coaching plan, you probably can make use of
    different forms of progressive overload depending on your goals.

    You could need to increase the volume, decrease rest, and
    try newer, more durable workout routines.
    You guessed it, figuring out a couple of muscle teams
    in a single workout! Training every muscle group twice allows you to break up your coaching
    quantity between different workouts.
    When you’re young, your physique runs at optimum levels and can recover comparatively easily, assuming you are consuming properly and getting sufficient sleep.
    Nevertheless, under regular situations, we expect that 3 to
    5 days is good for most. In addition to consuming well, sleep can be
    extremely important on your training outcomes.
    It should match individual anatomy, health levels,
    and personal objectives closely. Whether aiming for
    muscle gain, power, or endurance, efficient mixtures of muscle teams can optimize
    every fitness center session. Optimization Methods
    are essential when planning your exercise routine. Understanding which muscle
    group combos to focus on together can maximize your efficiency.
    Including compound and isolation movements ensures a full-range development.
    Compound exercises like deadlifts and chin-ups work multiple muscular tissues.
    Isolation strikes like concentration curls concentrate on just
    one muscle at a time.
    How many workout routines per muscle group you do is essential, but it doesn’t should be an actual number.
    Today, I Am Going To cowl every little thing you have to know to make one of the best decision for what quantity of workout
    routines per muscle group you should do. Different factors, including what kind of exercise you are
    choosing, your workout cut up, and the way often you work
    out matter too. Use a workout log to observe your power, repetitions, and general efficiency.

    Attempt to decide to at least three out of seven days a week for the
    most effective results. You ought to purpose to stimulate the assorted muscle groups with
    the right exercises to get essentially the most out of a exercise
    session. Coaching particular muscle groups collectively
    helps ensure stability during development. Keep Away From specializing in explicit muscle tissue over others, as this will result in overtraining
    and overdevelopment of those muscle tissue. An instance is when the legs are skinny and lack muscle tissue, but the arm, again and
    shoulder muscle tissue are muscular and bulging.
    I will say though, if you practice close to failure,
    you presumably can see great leads to muscle development
    doing as many as 25 reps per set. The burn gets fairly gnarly,
    however I’ve used it in my very own training and it
    really works as properly.
    But then you definitely step back and realise that
    although you understand precisely the method to practice
    each muscle, you don’t know when, how usually, and what muscle
    groups to coach together on the same day. What’s more, simply because you are
    doing body weight exercises doesn’t imply you will be doing extra
    total exercises per workout, however you might need to do more
    volume (reps and sets). Hold your workouts to 5-8 exercises and
    up the depth so each exercise and set is challenging sufficient to
    build muscle and energy. There are a lot of people out there who are beneath the
    impression that the extra time spent within the health club
    the better. A secondary approach to design a exercise
    coaching split, is by pairing muscle groups by movement or force.

    This type of resistance coaching pairing known as a push pull program, or push pull, legs program.
    Pairing chest and tricep workouts in a exercise is a
    suitable mixture that maximises efficiency.
    Well-liked choices include Push/Pull/Legs, Upper/Lower, Full Physique, and Bro Splits,
    every with its pros and cons. The secret is selecting a cut up that allows constant progression and suits particular person restoration wants.

    Many people swear by bro splits, however I don’t think they’re as unhealthy as they’re made
    out to be. Certain, science says training a muscle
    twice every week is «optimal,» but let’s be real—tons of bodybuilders have built insane physiques hitting every muscle
    once every week. I’d quite see somebody crush chest
    on Monday and take the relaxation of the week to get well correctly than half-ass it each different day.
    When designing a coaching cut up, give consideration to a couple of
    key principles. These principles ensure that your workouts are efficient and
    that you can get well properly.
    This interaction between completely different muscle
    teams makes it easier to mix them for significantly simpler
    exercises. Just looking at the 6 totally different groups, you’re most likely able to guess which of them should be targeted collectively throughout your power training periods.
    People are likely to divide the body’s muscular tissues into
    groups in several methods relying on their
    focus. Additionally, many experienced lifters cycle between totally different workout splits throughout the year, normally spending between 6-10 weeks on each, in accordance with their
    power training goals. When you start your chest workout routines day with a compound train like the chest
    press, your benching can be working your shoulder & triceps muscles in addition to your chest’s pectoral muscular tissues.

    The depth at which we exercise is the ultimate word consider figuring
    out our muscle growth and strength positive
    aspects. You have to problem your muscle teams, then allow them the proper time to get well so that you just’re prepared for the following exercise.
    One massive advantage of this particular cut up is that the biceps and
    triceps, smaller muscle groups that get well more quickly, get
    skilled twice over the split. This is a great technique should you’re in search of
    serious arm growth.
    Nevertheless, one massive problem is it’s not all the time obvious whether you getting enough
    relaxation. Your life-style will actually determine if lifting 6 days every week is sweet for you.
    For those who have good recovery practice,
    they can capitalize on protein synthesis with a 6 day cut
    up.
    This technique not only reduces the chance of burnout but
    also supports better performance in each exercise, making certain you get
    probably the most out of every set. This approach prevents any one muscle group from
    turning into overly fatigued and allows you to
    preserve a excessive degree of effort throughout the session.
    By often integrating balanced pairings, you build a well-rounded physique and improve overall performance.
    Focusing on complementary or opposing muscle groups ensures that either side of a joint or body space are equally skilled.

    This keeps your workout depth high with out extended relaxation periods.

    The exercises in this information are one of the best at
    focusing on their respective muscle teams and there are
    tons of variations of each one which you ought to use if you need a change.
    Embody them in your exercise routine for superior muscle activation and increased muscle mass.
    A favorite of lifters who get their routine finished from a home health club, you possibly can substitute the barbell in this train with any weighted object that
    you can keep in place. They also call this transfer a
    glute bridge because it builds so much strength there.
    Creating an efficient exercise routine entails understanding
    which muscle teams to train collectively. Focusing on complementary muscle teams not only optimizes
    your exercise effectivity but in addition helps in achieving balanced muscle growth and stopping
    accidents. Here’s an insightful exploration of the highest muscle groups to workout together.

    Rise until you’re as close to your knees as possible after which return to the starting place.
    Starting with the weights down by your sides, slowly carry till your thumbs are
    near your shoulders and your elbows are bent at a ninety-degree angle.
    If you’re new to weightlifting, you might wish to have a private trainer or extra skilled lifter close by to identify you.

    Take the barbell off the rack and maintain it together with your palms shoulder-width aside
    and going through the ceiling. As you’ll find a way to see, some of these muscles have proximity to one
    another that lends itself naturally to larger groupings.

    Creating a good workout plan means choosing the right exercises to construct muscle.
    Choosing the best muscle teams can change your fitness journey.
    It helps goal particular muscles with great precision and efficiency.
    Studies present attention-grabbing details about how muscles
    adapt and the way typically to coach. A 3-day
    break up workout plan is perfect as a end result of
    it balances hard training with relaxation.
    As the name suggest, a full physique exercise break up involves full body exercises for each of
    the three periods. Nonetheless, this doesn’t essentially mean you may be training
    each muscle group equally each session. Start your session with chest presses, which have interaction your
    pectoral muscular tissues whereas also involving your triceps and shoulders.

    Deciding what muscle teams to exercise collectively largely comes down what quantity of times per week you can prepare and
    how properly you recuperate. Help your lower body with your toes and ensure your elbows are immediately beneath your shoulders.
    Drive your elbows into the ground and interact your glutes, core, and quads.
    Maintain that position for as lengthy as you can before resting
    and repeating one or two occasions. Hammer curls activate the
    biceps, brachialis, and brachioradialis, three
    individual muscles which are hugely essential for shifting the elbow.
    You really have to make use of dumbbells for this move
    because kettlebells and different weights don’t allow for
    the mandatory wrist motion to occur.
    This is a favorite bodybuilding transfer but it might require building power with similar strikes just
    like the seated dumbbell shoulder press. As Soon As you do have the required strength and wrist mobility,
    though, the overhead press has tons of muscle-building potential.

    There’s no better method to work that particular muscle than pulldowns.
    This transfer supplies a lot of the identical advantages of a bench press with
    out requiring you to break type and regulate weights or
    fuss round with bumper plates. You’ll want dumbbells and an incline bench set between 45 and 60 degrees.
    It is also important for people to incorporate enough relaxation between workout days to keep away from overtraining.
    It may also be helpful to warm up earlier than exercising and to focus on good kind and technique whereas exercising.

    We provide the nutrients you have to power your active life-style.

    Your diet will play a big position in figuring out if you succeed with this program; nonetheless, you don’t must overcomplicate it.
    That stated, if you want to make up for a workout any given week, exceptions can be made.

    Don’t forget to include proper warm-ups and cool-downs to keep
    up flexibility and prevent injury. You can mix it up with
    completely different curl variations, like hammer curls or concentration curls, to hit the muscle from varied
    angles. Biacromial distance or width is just the width of your shoulders.

    «If you are training five or six occasions per week, a body-part split is greatest so as to allow adequate recovery of each muscle group between exercises,» Tumminello says.
    You need to train each body half at least two times a week and
    get 10 to twenty units per muscle group per week for finest results.
    For instance, many chest workout routines, like push-ups or bench presses, also engage the shoulders and triceps as secondary
    movers.
    For these critical about health, investing in squat racks, barbells, and weight plates can open up extra
    training choices. When training muscles strategically, it’s
    important to plan your progress. Bodybuilding
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    This burns fat in addition to building muscle for an optimally defined body.
    The six major muscle teams to focus on for a balanced exercise routine are the chest, back, shoulders,
    legs, arms, and core. Here’s an easy information to the best muscle group mixtures to workout
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    All The Time seek the guidance of with a qualified healthcare skilled previous to beginning any food plan or train program or taking any dietary supplement.
    The content material on our website is for informational and academic
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