Ифосфамид - алкилирующий цитостатик из группы азотистого иприта, производный оксазафосфоринов. Противоопухолевая активность ифосфамида обусловлена алкилированием нуклеофильных центров, нарушением синтеза ДНК и блокированием митотического деления опухолевых клеток. Повреждения ДНК наиболее часто происходят в фазах G1 и G2 клеточного цикла.
Показания к применению
Герминогенные опухоли
Рак яичников
Злокачественные опухоли яичка
Рак легкого
Рак молочной железы
Рак поджелудочной железы
Рак эндометрия
Рак шейки матки
Злокачественные лимфомы
Саркомы мягких тканей
Остеогенные саркомы
Опухоль Вильмса
Саркома Юинга
Противопоказания
Выраженное угнетение функции костного мозга
Выраженное нарушение функции почек
Обструкция мочевыводящих путей
Цистит
Беременность
Лактация
Повышенная чувствительность к ифосфамиду. С осторожностью: гипопротеинемия, гипоальбуминемия, нарушение электролитного баланса, пожилой возраст, иммунносупрессия, сахарный диабет, хроническая печеночная недостаточность, метастазы в головной мозг, церебральные симптомы, ветряная оспа (в т.ч. недавно перенесенная или после контакта с заболевшими), опоясывающий герпес, острые инфекционные заболевания
Применение при беременности и в период грудного вскармливания
Препарат противопоказан при беременности и в период лактации.
Способ применения и дозы
Ифосфамид входит в состав многих схем химиотерапевтического лечения, в связи с чем при выборе режима и доз в каждом индивидуальном случае следует руководствоваться данными специальной литературы. Препарат вводится в/в капельно в течение 30 мин или в виде 24-часовой инфузий. Используют раствор с концентрацией не выше 4%. — 1.2-2.4 г/л/сут в течение 3-5 дней подряд или через день до суммарной курсовой дозы 10-12 г/м2 курсы повторяют каждые 3 недели; — 3-5 г/м2 1 раз в 2 недели; — 5-8 г/м2 в виде 24-часовой инфузии 1 раз в 3-4 недели или по 3.2 г/м2/сут в виде 5-дневной непрерывной инфузии с интервалом в 3-4 недели. Для снижения вероятности возникновения геморрагического цистита одновременно с ифосфамидом применяют препарат месна в общей дозе, составляющей 60% от дозы ифосфамида. Приготовление раствора для в/в введения Порошок во флаконах растворяют в воде для инъекций до получения концентрации 40 мг/1 мл. Для в/в введения в течение 30 мин полученный раствор разводят в 500 мл 0.9% раствора натрия хлорида, раствора Рингера или 5% раствора декстрозы. Для введения препарата в виде 24-часовой инфузии, полученный раствор препарата разводят в 3 л 0.9% раствора натрия хлорида или 5% раствора декстрозы. Ифосфамид и месну можно смешивать в одном и том же растворе для инфузии.
Побочное действие
Со стороны системы кроветворения: лейкопения, тромбоцитопения, анемия. Самый низкий уровень количества лейкоцитов и тромбоцитов отмечается через 7-14 дней, восстановление картины крови происходит обычно через 21 день после окончания курса. Со стороны пищеварительной системы: тошнота и рвота; редко – стоматит, нарушение функции печени, обычно проявляющееся в виде повышения активности печеночных ферментов и/или уровня билирубина в сыворотке крови. Со стороны мочевыделительной системы: геморрагический цистит, дизурия, частое мочеиспускание и другие симптомы воспаления мочевого пузыря (кровь в моче, болезненное мочеиспускание), нарушение функции почек (повышение концентрации креатинина и мочевины в сыворотке крови, снижение клиренса креатинина. глюкозурия). Также может наблюдаться протеинурия и метаболический ацидоз. Со стороны ЦНС: дезориентация, спутанность сознания, галлюцинации, повышенная утомляемость, ажитация, энцефалопатия; менее часто - головокружение; редко - судорожные припадки, кома, периферическая полиневропатия. Со стороны репродуктивной системы: нарушение функции половых желез (азооспермия, аменорея). Со стороны кожи и кожных придатков: обратимая алопеция, фотосенсибилизация. Местные реакции: покраснение, отечность или боль в месте введения. Прочие: кардиотоксическое действие, иммуносупрессия, инфекционные осложнения, замедление скорости заживления ран, легочные симптомы (кашель или одышка), повышение температуры тела, аллергические реакции.
Передозировка
Симптомы: более быстрое развитие и резкая выраженность основных побочных эффектов. Лечение: симптоматическое, с обязательным использованием месны.
Особые указания
Перед началом лечения необходима санация очагов хронической инфекции и коррекция возможных нарушений электролитного баланса. Во время лечения препаратом необходимо регулярно контролировать картину периферической крови (особенно, обращая внимание на число нейтрофилов и тромбоцитов), лабораторные показатели функции печени, почек, а также регулярно проводить анализ мочи на наличие эритроцитов, появление которых может предшествовать развитию геморрагического цистита. Женщинам и мужчинам во время лечения и втечение 3-х месяцев после окончания терапии ифосфамидом следует использовать надежные способы контрацепции. При нарушении функции почек и оттока мочи, возможно повышение частоты токсического действия препарата на ЦНС, в связи с чем может возникнуть необходимость снижения дозы ифосфамида. Для обеспечения выведения мочевой кислоты больным следует потреблять достаточное количество жидкости. При появлении первых признаков воспаления мочевого пузыря или появления крови в моче, терапия ифосфамидом должна быть прекращена. При лечении ифосфамидом возможно подавление естественных защитных механизмов, выработка антител в организме больного в ответ на введение вакцин может снижаться. Влияние на способность к вождению автотранспорта и управлению механизмами Во время проведения терапии препаратом Холоксан могут возникнуть тошнота и рвота, а также явления энцефалопатии, что может влиять на способность управлять автомобилем или работать с другими механизмами. Потому следуeт воздержаться от управления автомобилем и другими транспортными средствами. Не следует также работать с электрическими инструментами и механизмами.
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