Противоопухолевое средство. Предполагаемый механизм действия... Инструкция
Показания к применению
Хронический миелолейкоз - Истинная полицитемия (эритремия) - Эссенциальная тромбоцитемия - Остеомиелофиброз - Меланома - Злокачественные опухоли головы и шеи, за исключением рака губы (в комбинации с лучевой терапией) - Рак шейки матки (в комбинации с лучевой терапией)
Противопоказания
Повышенная чувствительность к гидроксикарбамиду или любому другому вспомогательному веществу, входящему в состав препарата. - Беременность и период грудного вскармливания. - Лейкопения ниже 2500/мкл, тромбоцитопения ниже 100000/мкл. - Детский возраст (безопасность и эффективность применения не установлена).
Действующее вещество: Гидроксикарбамид (Hydroxycarbamidum)Концентрация действующего вещества (мг): 500
Фармакологические свойства
Противоопухолевое средство. Предполагаемый механизм действия заключается в торможении синтеза ДНК. Не оказывает влияния на синтез белка и РНК.
Показания к применению
Хронический миелолейкоз - Истинная полицитемия (эритремия) - Эссенциальная тромбоцитемия - Остеомиелофиброз - Меланома - Злокачественные опухоли головы и шеи, за исключением рака губы (в комбинации с лучевой терапией) - Рак шейки матки (в комбинации с лучевой терапией)
Противопоказания
Повышенная чувствительность к гидроксикарбамиду или любому другому вспомогательному веществу, входящему в состав препарата. - Беременность и период грудного вскармливания. - Лейкопения ниже 2500/мкл, тромбоцитопения ниже 100000/мкл. - Детский возраст (безопасность и эффективность применения не установлена).
Применение при беременности и в период грудного вскармливания
Гидроксикарбамид противопоказан при беременности. При необходимости применения в период лактации следует прекратить грудное вскармливание. Женщины детородного возраста, получающие терапию гидроксикарбамидом, должны применять надежные методы контрацепции. В экспериментальных исследованиях установлено тератогенное и эмбриотоксическое действие гидроксикарбамида.
Способ применения и дозы
При выборе режима и доз в каждом индивидуальном случае следует руководствоваться данными специальной литературы. Препарат применяют внутрь. При затруднении глотания капсулу можно вскрыть, высыпать содержимое в стакан воды и немедленно выпить. При этом некоторые водонерастворимые вспомогательные вещества могут оставаться на поверхности раствора. Во время лечения препаратом следует принимать достаточно большое количество жидкости. Резистентный хронический миелолейкоз Непрерывная терапия. От 20 до 30 мг/кг ежедневно один раз в день. Оценку эффективности препарата проводят после 6 недель лечения. При приемлемом клиническом ответе лечение можно продолжать неограниченно долго. Лечение следует приостановить, если содержание лейкоцитов - менее 2500/мм3 или содержание тромбоцитов - менее 100000/мм3. Через 3 дня повторно проводят анализ крови. Лечение возобновляют тогда, когда содержание лейкоцитов и эритроцитов повышается до приемлемого (см. выше). Обычно восстановление содержания лейкоцитов и эритроцитов происходит достаточно быстро, в противном случае при совместном применении препарата с лучевой терапией, последняя может быть также приостановлена. Развитие анемии, даже тяжелой, не требует прерывания курса лечения при условии адекватной терапии (трансфузия эритроцитарной массы). Истинная полицитемия Лечение начинают с суточной дозы 15–20 мг/кг. Дозу устанавливают индивидуально, стремясь поддерживать гематокрит на уровне ниже 45%, а число тромбоцитов - ниже 400000/мкл. У большинства больных удается достигнуть этих показателей, постоянно применяя гидроксикарбамид в суточной дозе от 500 до 1000 мг. Эссенциальная тромбоцитемия Обычно назначают препарат Гидреа в начальной суточной дозе 15 мг/кг; затем подбирают такую дозу, которая поддерживает число тромбоцитов на уровне ниже 600000/мкл, не приводя при этом к уменьшению числа лейкоцитов ниже 4000/мкл. Солидные опухоли, меланома Прерывистая терапия: - 80 мг/кг один раз в день каждые три дня (6–7 доз) Непрерывная терапия: - 20–30 мг/кг ежедневно один раз в день в течение 3-х недель. Карцинома головы и шеи, карцинома шейки матки 80 мг/кг один раз в день, каждые три дня в комбинации с лучевой терапией. Лечение препаратом начинают не менее чем за 7 дней до начала лучевой терапии и продолжают во время лучевой терапии. После лучевой терапии препарат продолжают принимать в течение неограниченного времени при строгом наблюдении за больным и при отсутствии у него необычных или тяжелых токсических реакций. Пациенты с нарушением функции печени Указания по изменению доз у этой группы пациентов отсутствуют. Следует проводить тщательный мониторинг показателей крови у пациентов с нарушением функции печени. Пациенты с нарушением функции почек Поскольку гидроксимочевина выводится преимущественно через почки, необходимо снижение дозы при назначении препарата таким пациентам. Больным с почечной недостаточностью (клиренс креатинина менее 60 мл/мин) препарат обычно назначается в дозе 15 мг/кг. Больным в терминальной стадии почечной недостаточности препарат назначается в дозе 15 мг/кг дважды, с интервалом в 7 дней между приемами: первый раз - по окончании 4-х-часового сеанса гемодиализа, второй раз - перед проведением сеанса гемодиализа. Пожилые пациенты Поскольку у пожилых пациентов вероятность развития побочных эффектов при применении препарата Гидреа выше, чем у пациентов молодого возраста, рекомендуемая доза для пациентов этой группы не должна превышать 60 мг/кг в сутки.
Побочное действие
Инфекции: частота неизвестна - гангрена; Со стороны органов кроветворения: частота неизвестна - подавление функции костного мозга (лейкопения, анемия, тромбоцитопения). Со стороны органов пищеварения: частота неизвестна - гепатотоксичность, и панкреатит, иногда с летальным исходом (у ВИЧ-инфицированных пациентов, одновременно получаюших антиретровирусную терапию, в частности, диданозин и ставудин); стоматит, анорексия, тошнота, рвота, диарея, запор, мукозит, диспепсия, раздражение слизистой оболочки желудка, изъязвление слизистой оболочки желудочно-кишечного тракта; повышение активности «печеночных» ферментов и концентрации билирубина в плазме; Со стороны кожи и кожных придатков: частота неизвестна - кожный васкулит, макулезно-папулезные высыпания, эритема лица и периферическая эритема, изъязвления на коже, дерматомиозитоподобные изменения кожи, эксфолиация кожи, гиперпигментация, эритема, атрофия кожи и ногтей, шелушение, папулы фиолетового цвета, кожные токсические васкулиты (включая васкулитные изъязвления и гангрену); редко - алопеция, рак кожи. Со стороны нервной системы: частота неизвестна - головокружение, сонливость, дезориентация; головная боль, галлюцинации, судороги, периферическая нейропатия (у ВИЧ-инфицированных пациентов, одновременно получаюших антиретровирусную терапию, в частности, диданозин и ставудин), повышенная утомляемость,; Со стороны респираторной системы: частота неизвестна - фиброз легких, диффузная инфильтрация легких, одышка. Со стороны мочевыделительной системы: частота неизвестна - увеличение содержания мочевой кислоты в сыворотке крови, повышение содержания азота мочевины и креатинина в плазме крови, задержка мочи, интерстициальный нефрит, редко - дизурия. Прочие: частота неизвестна - озноб, лихорадка, общее недомогание, повышение СОЭ, кожные аллергические реакции, астения, редко - диффузная инфильтрация легких, одышка. Случаи развития панкреатита и гепатотоксичности (с возможным смертельным исходом), а также тяжелой периферической нейропатии отмечены у больных ВИЧ, которые принимали гидроксикарбамид совместно с антиретровирусными препаратами, в частности диданозин в комбинации со ставудином или без него. Побочные явления, наблюдаемые при одновременном применении гидроксикарбамида и лучевой терапии, такие же, как и при монотерапии препаратом, главным образом угнетение функции костного мозга (лейкопения, анемия) и раздражение слизистой оболочки желудка. Прием гидроксикарбамида может усиливать некоторые побочные эффекты, которые наблюдаются при лучевой терапии, такие как дискомфорт в желудке и мукозит.
Передозировка
Превышение рекомендуемых доз Гидреа проявляется изменениями слизистых и кожи, болезненностью кожи, фиолетовой эритемой, отеками и шелушением конечностей, острым стоматитом и гиперпигментацией кожи.
Особые указания
Для пациентов пожилого возраста может потребоваться коррекция режима дозирования. При применении гидроксикарбамида у пациентов с подагрой или нефролитиазом повышается риск возникновения гиперурикемии. Комбинация с лучевой терапией может приводить к усилению побочных эффектов, которые связаны с миелодепрессией и поражением слизистой желудка. Может усиливаться эритема, вызываемая облучением. Тошнота, рвота, анорексия, вызываемые комбинированным применением с лучевой терапией, в результате временной отмены гидроксикарбамида могут исчезнуть. Перед началом и во время лечения следует провести определение полной картины крови, включая исследование костного мозга, а также функции почек и печени. Анализ крови повторять не менее 1 раза/нед. При снижении числа лейкоцитов менее 2500/мкл, а тромбоцитов менее 100 000/мкл лечение следует прекратить до восстановления нормальных значений этих показателей. Возможны изменения СОЭ (чаще повышение). При развитии анемии ее следует лечить, не прерывая курса гидроксикарбамида, с помощью замещающих трансфузий эритроцитарной массы. Возможны изменения биохимических показателей: повышение концентрации в крови мочевины, креатинина, мочевой кислоты, повышение активности печеночных трансаминаз. Не рекомендуют проводить вакцинацию пациентов и членов их семей.
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Предполагаемый механизм действия заключается в торможении синтеза ДНК. Не оказывает влияния на синтез белка и РНК."}}]},{"id":3,"name":"Показания к применению","slug":"indications","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Хронический миелолейкоз - Истинная полицитемия (эритремия) - Эссенциальная тромбоцитемия - Остеомиелофиброз - Меланома - Злокачественные опухоли головы и шеи, за исключением рака губы (в комбинации с лучевой терапией) - Рак шейки матки (в комбинации с лучевой терапией)"}}]},{"id":4,"name":"Противопоказания","slug":"contraindications","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Повышенная чувствительность к гидроксикарбамиду или любому другому вспомогательному веществу, входящему в состав препарата. - Беременность и период грудного вскармливания. - Лейкопения ниже 2500/мкл, тромбоцитопения ниже 100000/мкл. - Детский возраст (безопасность и эффективность применения не установлена)."}}]},{"id":5,"name":"Применение при беременности и в период грудного вскармливания","slug":"pregnancy_warnings","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Гидроксикарбамид противопоказан при беременности. При необходимости применения в период лактации следует прекратить грудное вскармливание. Женщины детородного возраста, получающие терапию гидроксикарбамидом, должны применять надежные методы контрацепции. В экспериментальных исследованиях установлено тератогенное и эмбриотоксическое действие гидроксикарбамида."}}]},{"id":6,"name":"Способ применения и дозы","slug":"dosage","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"При выборе режима и доз в каждом индивидуальном случае следует руководствоваться данными специальной литературы. Препарат применяют внутрь. При затруднении глотания капсулу можно вскрыть, высыпать содержимое в стакан воды и немедленно выпить. При этом некоторые водонерастворимые вспомогательные вещества могут оставаться на поверхности раствора. Во время лечения препаратом следует принимать достаточно большое количество жидкости. Резистентный хронический миелолейкоз Непрерывная терапия. От 20 до 30 мг/кг ежедневно один раз в день. Оценку эффективности препарата проводят после 6 недель лечения. При приемлемом клиническом ответе лечение можно продолжать неограниченно долго. Лечение следует приостановить, если содержание лейкоцитов - менее 2500/мм3 или содержание тромбоцитов - менее 100000/мм3. Через 3 дня повторно проводят анализ крови. Лечение возобновляют тогда, когда содержание лейкоцитов и эритроцитов повышается до приемлемого (см. выше). Обычно восстановление содержания лейкоцитов и эритроцитов происходит достаточно быстро, в противном случае при совместном применении препарата с лучевой терапией, последняя может быть также приостановлена. Развитие анемии, даже тяжелой, не требует прерывания курса лечения при условии адекватной терапии (трансфузия эритроцитарной массы). Истинная полицитемия Лечение начинают с суточной дозы 15–20 мг/кг. Дозу устанавливают индивидуально, стремясь поддерживать гематокрит на уровне ниже 45%, а число тромбоцитов - ниже 400000/мкл. У большинства больных удается достигнуть этих показателей, постоянно применяя гидроксикарбамид в суточной дозе от 500 до 1000 мг. Эссенциальная тромбоцитемия Обычно назначают препарат Гидреа в начальной суточной дозе 15 мг/кг; затем подбирают такую дозу, которая поддерживает число тромбоцитов на уровне ниже 600000/мкл, не приводя при этом к уменьшению числа лейкоцитов ниже 4000/мкл. Солидные опухоли, меланома Прерывистая терапия: - 80 мг/кг один раз в день каждые три дня (6–7 доз) Непрерывная терапия: - 20–30 мг/кг ежедневно один раз в день в течение 3-х недель. Карцинома головы и шеи, карцинома шейки матки 80 мг/кг один раз в день, каждые три дня в комбинации с лучевой терапией. Лечение препаратом начинают не менее чем за 7 дней до начала лучевой терапии и продолжают во время лучевой терапии. После лучевой терапии препарат продолжают принимать в течение неограниченного времени при строгом наблюдении за больным и при отсутствии у него необычных или тяжелых токсических реакций. Пациенты с нарушением функции печени Указания по изменению доз у этой группы пациентов отсутствуют. Следует проводить тщательный мониторинг показателей крови у пациентов с нарушением функции печени. Пациенты с нарушением функции почек Поскольку гидроксимочевина выводится преимущественно через почки, необходимо снижение дозы при назначении препарата таким пациентам. Больным с почечной недостаточностью (клиренс креатинина менее 60 мл/мин) препарат обычно назначается в дозе 15 мг/кг. Больным в терминальной стадии почечной недостаточности препарат назначается в дозе 15 мг/кг дважды, с интервалом в 7 дней между приемами: первый раз - по окончании 4-х-часового сеанса гемодиализа, второй раз - перед проведением сеанса гемодиализа. Пожилые пациенты Поскольку у пожилых пациентов вероятность развития побочных эффектов при применении препарата Гидреа выше, чем у пациентов молодого возраста, рекомендуемая доза для пациентов этой группы не должна превышать 60 мг/кг в сутки."}}]},{"id":7,"name":"Побочное действие","slug":"side_effects","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Инфекции: частота неизвестна - гангрена; Со стороны органов кроветворения: частота неизвестна - подавление функции костного мозга (лейкопения, анемия, тромбоцитопения). Со стороны органов пищеварения: частота неизвестна - гепатотоксичность, и панкреатит, иногда с летальным исходом (у ВИЧ-инфицированных пациентов, одновременно получаюших антиретровирусную терапию, в частности, диданозин и ставудин); стоматит, анорексия, тошнота, рвота, диарея, запор, мукозит, диспепсия, раздражение слизистой оболочки желудка, изъязвление слизистой оболочки желудочно-кишечного тракта; повышение активности «печеночных» ферментов и концентрации билирубина в плазме; Со стороны кожи и кожных придатков: частота неизвестна - кожный васкулит, макулезно-папулезные высыпания, эритема лица и периферическая эритема, изъязвления на коже, дерматомиозитоподобные изменения кожи, эксфолиация кожи, гиперпигментация, эритема, атрофия кожи и ногтей, шелушение, папулы фиолетового цвета, кожные токсические васкулиты (включая васкулитные изъязвления и гангрену); редко - алопеция, рак кожи. Со стороны нервной системы: частота неизвестна - головокружение, сонливость, дезориентация; головная боль, галлюцинации, судороги, периферическая нейропатия (у ВИЧ-инфицированных пациентов, одновременно получаюших антиретровирусную терапию, в частности, диданозин и ставудин), повышенная утомляемость,; Со стороны респираторной системы: частота неизвестна - фиброз легких, диффузная инфильтрация легких, одышка. Со стороны мочевыделительной системы: частота неизвестна - увеличение содержания мочевой кислоты в сыворотке крови, повышение содержания азота мочевины и креатинина в плазме крови, задержка мочи, интерстициальный нефрит, редко - дизурия. Прочие: частота неизвестна - озноб, лихорадка, общее недомогание, повышение СОЭ, кожные аллергические реакции, астения, редко - диффузная инфильтрация легких, одышка. Случаи развития панкреатита и гепатотоксичности (с возможным смертельным исходом), а также тяжелой периферической нейропатии отмечены у больных ВИЧ, которые принимали гидроксикарбамид совместно с антиретровирусными препаратами, в частности диданозин в комбинации со ставудином или без него. Побочные явления, наблюдаемые при одновременном применении гидроксикарбамида и лучевой терапии, такие же, как и при монотерапии препаратом, главным образом угнетение функции костного мозга (лейкопения, анемия) и раздражение слизистой оболочки желудка. Прием гидроксикарбамида может усиливать некоторые побочные эффекты, которые наблюдаются при лучевой терапии, такие как дискомфорт в желудке и мукозит."}}]},{"id":8,"name":"Передозировка","slug":"overdose","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Превышение рекомендуемых доз Гидреа проявляется изменениями слизистых и кожи, болезненностью кожи, фиолетовой эритемой, отеками и шелушением конечностей, острым стоматитом и гиперпигментацией кожи."}}]},{"id":9,"name":"Особые указания","slug":"cautions","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Для пациентов пожилого возраста может потребоваться коррекция режима дозирования. При применении гидроксикарбамида у пациентов с подагрой или нефролитиазом повышается риск возникновения гиперурикемии. Комбинация с лучевой терапией может приводить к усилению побочных эффектов, которые связаны с миелодепрессией и поражением слизистой желудка. Может усиливаться эритема, вызываемая облучением. Тошнота, рвота, анорексия, вызываемые комбинированным применением с лучевой терапией, в результате временной отмены гидроксикарбамида могут исчезнуть. Перед началом и во время лечения следует провести определение полной картины крови, включая исследование костного мозга, а также функции почек и печени. Анализ крови повторять не менее 1 раза/нед. При снижении числа лейкоцитов менее 2500/мкл, а тромбоцитов менее 100 000/мкл лечение следует прекратить до восстановления нормальных значений этих показателей. Возможны изменения СОЭ (чаще повышение). При развитии анемии ее следует лечить, не прерывая курса гидроксикарбамида, с помощью замещающих трансфузий эритроцитарной массы. Возможны изменения биохимических показателей: повышение концентрации в крови мочевины, креатинина, мочевой кислоты, повышение активности печеночных трансаминаз. 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