Дифлюкан Раствор, 100 мл, 2 мг/мл, для внутривенного введения

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Механизмы развития резистентности к флуконазолу Резистентность к флуконазолу может развиться в следующих случаях: качественное или количественное изменение фермента, являющегося мишенью для флуконазола (ланостерил 14-?-деметилазы), уменьшение доступа к мишени флуконазола или комбинация этих механизмов. Точечные мутации в гене ERG11, кодирующем фермент-мишень, приводят к видоизменению мишени и снижению аффинности к азолам. Увеличение экспрессии гена ERG11 приводит к продукции высоких концентраций фермента-мишени, что создает потребность в увеличении концентрации флуконазола во внутриклеточной жидкости для подавления всех молекул фермента в клетке. Второй значительный механизм резистентности заключается в активном выведении флуконазола из внутриклеточного пространства посредством активации двух типов транспортеров, участвующих в активном выведении (эффлюксе) препаратов из грибковой клетки. К таким транспортерам относится главный посредник, кодируемый генами MDR (множественной лекарственной устойчивости), и суперсемейство АТФ-связывающей кассеты транспортеров, кодируемое генами CDR (генами резистентности грибов Candida spp. к азоловым антимикотикам). Гиперэкспрессия гена MDR приводит к резистентности к флуконазолу, в то же время гиперэкспрессия генов CDR может приводить к резистентности к различным азолам. Резистентность к Candida glabrata обычно опосредована гиперэкспрессией гена CDR, что приводит к резистентности ко многим азолам. Для тех штаммов, у которых МИК определяется как промежуточная (16-32 мкг/мл) рекомендуется применять максимальные дозы флуконазола. Candida krusei следует рассматривать как возбудитель, резистентный к флуконазолу. Механизм резистентности связан со сниженной чувствительностью фермента-мишени к ингибирующему воздействию флуконазола."}}]},{"id":3,"name":"Показания к применению","slug":"indications","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Киптококкоз, включая криптококковый менингит и инфекции другой локализации (например, легких, кожи), в т.ч. у больных с нормальным иммунным ответом и у больных СПИД, реципиентов пересаженных органов и больных с другими формами иммунодефицита . поддерживающая терапия с целью профилактики рецидивов криптококкоза у больных СПИД . генерализованный кандидоз, включая кандидемию, диссеминированный кандидоз и другие формы инвазивной кандидозной инфекции, такие как инфекции брюшины, эндокарда, глаз, дыхательных и мочевых путей, в т.ч. у больных со злокачественными опухолями, находящихся в ОИТ и получающих цитотоксические или иммуносупрессивные средства, а также у больных с другими факторами, предрасполагающими к развитию кандидоза . кандидоз слизистых оболочек, включая слизистые оболочки полости рта и глотки, пищевода, неинвазивные бронхолегочные инфекции, кандидурия, кожно-слизистый и хронический атрофический кандидоз полости рта (связанный с ношением зубных протезов), в т.ч. у больных с нормальной и подавленной иммунной функцией . профилактика рецидива орофарингеального кандидоза у больных СПИД . генитальный кандидоз . острый или рецидивирующий вагинальный кандидоз . профилактика с целью уменьшения частоты рецидивов вагинального кандидоза (3 и более эпизодов в год) . кандидозный баланит . профилактика грибковых инфекций у больных со злокачественными опухолями, предрасположенных к развитию таких инфекций в результате цитотоксической химиотерапии или лучевой терапии . микозы кожи, включая микозы стоп, тела, паховой области, отрубевидный лишай, онихомикозы и кожные кандидозные инфекции . глубокие эндемические микозы у больных с нормальным иммунитетом, кокцидиоидомикоз, паракокцидиоидомикоз, споротрихоз и гистоплазмоз."}}]},{"id":4,"name":"Противопоказания","slug":"contraindications","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Одновременное применение терфенадина во время многократного применения флуконазола в дозе 400 мг/сут и более . одновременное применение с препаратами, увеличивающими интервал QT и метаболизирующимися с помощью изофермента CYP3A4, такими как цизаприд, астемизол, эритромицин, пимозид и хинидин . дефицит сахаразы/изомальтазы, непереносимость фруктозы, глюкозо-галактозная мальабсорбция (для порошка для приготовления суспензии) .— непереносимость галактозы, лактазная недостаточность и нарушение всасывания глюкозы/галактозы (для капсул) . детский возраст до 3 лет (для капсул) . повышенная чувствительность к флуконазолу, другим компонентам препарата или азольным веществам со сходной с флуконазолом структурой."}}]},{"id":5,"name":"Применение при беременности и в период грудного вскармливания","slug":"pregnancy_warnings","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Адекватных и контролируемых исследований безопасности применения препарата у беременных женщин не проводилось. Описаны случаи множественных врожденных пороков у новорожденных, матери которых в течение 3 и более месяцев получали терапию флуконазолом в высокой дозе (400-800 мг/сут) по поводу кокцидиоидомикоза. Были отмечены следующие нарушения развития: брахицефалия, нарушение развития лицевой части черепа, нарушение формирования свода черепа, волчья пасть, искривление бедренных костей, истончение и удлинение ребер, артрогрипоз и врожденные пороки сердца. В настоящее время нет доказательств связи перечисленных врожденных нарушений с применением флуконазола в низких дозах (150 мг однократно для лечения вульвовагинального кандидоза) в I триместре беременности. Следует избегать применения флуконазола при беременности, за исключением случаев тяжелых и потенциально угрожающих жизни грибковых инфекций, когда ожидаемая польза лечения превышает возможный риск для плода. Поэтому женщинам детородного возраста следует использовать надежные средства контрацепции. Флуконазол обнаруживают в грудном молоке в концентрациях, близких к плазменным, поэтому применять Дифлюкан . в период лактации (грудного вскармливания) не рекомендуется."}}]},{"id":6,"name":"Побочное действие","slug":"side_effects","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Наиболее часто встречались побочные эффекты, которые были зарегистрированы в клинических и постмаркетинговых (*) исследованиях препарата Дифлюкан .. Со стороны нервной системы: головная боль, головокружение*, судороги*, изменение вкуса*, парестезия, бессонница, сонливость, тремор. Со стороны пищеварительной системы: боль в животе, диарея, метеоризм, тошнота, диспепсия*, рвота*, сухость слизистой оболочки полости рта, запор, гепатотоксичность (в некоторых случаях с летальным исходом), повышение концентрации билирубина, сывороточной активности АЛТ и АСТ, ЩФ, нарушение функции печени*, гепатит*, гепатоцеллюлярный некроз*, желтуха*, холестаз, гепатоцеллюлярное повреждение. Со стороны сердечно-сосудистой системы*: увеличение интервала QT на ЭКГ, аритмия, в т.ч. желудочковая тахисистолическая типа \"пируэт\". Со стороны кожных покровов: сыпь, алопеция*, эксфолиативные кожные заболевания*, включая синдром Стивенса-Джонсона и токсический эпидермальный некролиз, острый генерализованный экзантематозный пустулез, повышенное потоотделение, лекарственная сыпь. Со стороны системы кроветворения*: лейкопения, включая нейтропению и агранулоцитоз, тромбоцитопения, анемия. Со стороны обмена веществ*: повышение уровня холестерина и триглицеридов в плазме, гипокалиемия. Со стороны костно-мышечной системы: миалгия. Аллергические реакции*: анафилактические реакции (включая ангионевротический отек, отек лица, крапивница, зуд). Прочие: слабость, астения, повышенная утомляемость, лихорадка, вертиго. У некоторых больных, особенно с серьезными заболеваниями (СПИД, злокачественные новообразования), при лечении препаратом Дифлюкан . и сходными препаратами наблюдались изменения показателей крови, функции почек и печени, однако клиническое значение этих изменений и их связь с лечением не установлены. Переносимость препарата обычно очень хорошая."}}]},{"id":7,"name":"Особые указания","slug":"cautions","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Наиболее часто встречались побочные эффекты, которые были зарегистрированы в клинических и постмаркетинговых (*) исследованиях препарата Дифлюкан .. Со стороны нервной системы: головная боль, головокружение*, судороги*, изменение вкуса*, парестезия, бессонница, сонливость, тремор. Со стороны пищеварительной системы: боль в животе, диарея, метеоризм, тошнота, диспепсия*, рвота*, сухость слизистой оболочки полости рта, запор, гепатотоксичность (в некоторых случаях с летальным исходом), повышение концентрации билирубина, сывороточной активности АЛТ и АСТ, ЩФ, нарушение функции печени*, гепатит*, гепатоцеллюлярный некроз*, желтуха*, холестаз, гепатоцеллюлярное повреждение. Со стороны сердечно-сосудистой системы*: увеличение интервала QT на ЭКГ, аритмия, в т.ч. желудочковая тахисистолическая типа \"пируэт\". Со стороны кожных покровов: сыпь, алопеция*, эксфолиативные кожные заболевания*, включая синдром Стивенса-Джонсона и токсический эпидермальный некролиз, острый генерализованный экзантематозный пустулез, повышенное потоотделение, лекарственная сыпь. Со стороны системы кроветворения*: лейкопения, включая нейтропению и агранулоцитоз, тромбоцитопения, анемия. Со стороны обмена веществ*: повышение уровня холестерина и триглицеридов в плазме, гипокалиемия. Со стороны костно-мышечной системы: миалгия. Аллергические реакции*: анафилактические реакции (включая ангионевротический отек, отек лица, крапивница, зуд). Прочие: слабость, астения, повышенная утомляемость, лихорадка, вертиго. У некоторых больных, особенно с серьезными заболеваниями (СПИД, злокачественные новообразования), при лечении препаратом Дифлюкан . и сходными препаратами наблюдались изменения показателей крови, функции почек и печени, однако клиническое значение этих изменений и их связь с лечением не установлены. Переносимость препарата обычно очень хорошая."}}]}],"source":{"title":"36.6","url":"https://366.ru"}},"description_toggle":false,"short_description":"Противогрибковый препарат триазольного ряда, является мощным селективным ингибитором синтеза стеролов в клетке грибов. Показана активность флуконазола in vitro и при клинических инфекциях в отношении большинства следующих микроорганизмов: Candida alhicans, Candida glabrata (многие штаммы умеренно чувствительны), Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans. Была показана активность флуконазола in vitro в отношении следующих микроорганизмов, однако клиническое значение этого неизвестно: Candida dubliniensis, Candida guilliermondii, Candida kefyr, Candida lusitaniae. При приеме внутрь и при в/в введении флуконазол проявлял активность на различных моделях грибковых инфекций у животных. Продемонстрирована активность препарата при оппортунистических микозах, в т.ч. вызванных Candida spp. (включая генерализованный кандидоз у животных со сниженным иммунитетом), Cryptococcus neoformans (включая внутричерепные инфекции), Microsporum spp. и Trychoptyton spp. Установлена также активность флуконазола на моделях эндемических микозов у животных, включая инфекции, вызванные Blastomyces dermatitidis, Coccidioides immitis (включая внутричерепные инфекции) и Histoplasma capsulatum у животных с нормальным и со сниженным иммунитетом. Флуконазол обладает высокой специфичностью в отношении грибковых ферментов, зависимых от цитохрома P450. Терапия флуконазолом по 50 мг/сут в течение до 28 суток не влияет на концентрацию тестостерона в плазме у мужчин или концентрацию стероидов у женщин детородного возраста. Флуконазол в дозе 200-400 мг/сут не оказывал клинически значимого влияния на уровни эндогенных стероидов и их реакцию на стимуляцию АКТГ у здоровых мужчин-добровольцев. Механизмы развития резистентности к флуконазолу Резистентность к флуконазолу может развиться в следующих случаях: качественное или количественное изменение фермента, являющегося мишенью для флуконазола (ланостерил 14-?-деметилазы), уменьшение доступа к мишени флуконазола или комбинация этих механизмов. Точечные мутации в гене ERG11, кодирующем фермент-мишень, приводят к видоизменению мишени и снижению аффинности к азолам. Увеличение экспрессии гена ERG11 приводит к продукции высоких концентраций фермента-мишени, что создает потребность в увеличении концентрации флуконазола во внутриклеточной жидкости для подавления всех молекул фермента в клетке. Второй значительный механизм резистентности заключается в активном выведении флуконазола из внутриклеточного пространства посредством активации двух типов транспортеров, участвующих в активном выведении (эффлюксе) препаратов из грибковой клетки. К таким транспортерам относится главный посредник, кодируемый генами MDR (множественной лекарственной устойчивости), и суперсемейство АТФ-связывающей кассеты транспортеров, кодируемое генами CDR (генами резистентности грибов Candida spp. к азоловым антимикотикам). Гиперэкспрессия гена MDR приводит к резистентности к флуконазолу, в то же время гиперэкспрессия генов CDR может приводить к резистентности к различным азолам. Резистентность к Candida glabrata обычно опосредована гиперэкспрессией гена CDR, что приводит к резистентности ко многим азолам. Для тех штаммов, у которых МИК определяется как промежуточная (16-32 мкг/мл) рекомендуется применять максимальные дозы флуконазола. Candida krusei следует рассматривать как возбудитель, резистентный к флуконазолу. Механизм резистентности связан со сниженной чувствительностью фермента-мишени к ингибирующему воздействию флуконазола.","substance":[{"id":71,"title":"Флуконазол","title_latin":"Fluconazolum","slug":"flukonazol_71"}],"branding":null,"valid_for_quick_buy":false,"is_available_to_delivery":false,"comments":null,"image_alt":"Дифлюкан - фото упаковки","image_share":{"isTouch":{"default":"https://vseapteki.ru/cropping/thumbnails/101/10641/share_default/"},"isFromTablet":{"default":"https://vseapteki.ru/cropping/thumbnails/101/10641/share_default/"}},"diseases":[{"id":"113","title":"Болезнь, вызванная вирусом иммунодефицита человека [ВИЧ], проявляющаяся в виде инфекционных и паразитарных болезней","slug":"113-bolezn_vyzvannaya_virusom_immunodefitsita_cheloveka_vich_proyavlyayuschayasya_v_vide_infektsionnyh_i_parazitarnyh_bolezney"},{"id":"115","title":"Болезнь, вызванная ВИЧ, с проявлениями кандидоза","slug":"115-bolezn_vyzvannaya_vich_s_proyavleniyami_kandidoza"},{"id":"131","title":"Микоз 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