язвенная болезнь желудка и двенадцатиперстной кишки (лечение и эрадикационная терапия инфекции Helicobacter pylori).
Фармакологическое действие
Тройная терапия, включающая кларитромицин, амоксициллин и лансопразол, позволяет достичь высокий процент эрадикации Helicobacter pylori (85-94%).
Кларитромицин
При совместном приеме кларитромицина и лекарственных средств, первично метаболизирующихся изоферментами CYP3A, возможно взаимное повышение их концентраций, что может усилить или продлить как терапевтические, так и побочные эффекты. Противопоказан совместный прием с астемизолом, цизапридом, пимозидом, терфенадином, эрготамином и другими алкалоидами спорыньи, алпразоламом, мидазоламом, триазоламом. С осторожностью назначают с карбамазепином, цилостазолом, циклоспорином, дизопирамидом, ловастатином, метилпреднизолоном, омепразолом, непрямыми антикоагулянтами (в том числе варфарином), хинидином, рифабутином, силденафилом, симвастатином, такролимусом, винбластином, фенитоином, теофиллином и вальпроевой кислотой (метаболизируются через другие изоферменты цитохрома Р450). Необходима коррекция дозы лекарственных средств и контроль концентрации в плазме крови. При совместном применении с цизапридом, пимозидом, терфенадином и астемизолом возможно увеличение концентрации последних в плазме крови, удлинение интервала QTи развитие сердечных аритмий, включая желудочковую пароксизмальную тахикардию, фибрилляцию, трепетание или мерцание желудочков, полиморфную желудочковую тахикардию по типу «пируэт» (см. раздел «Противопоказания»). Подобный механизм взаимодействия отмечается при применении лекарственных препаратов, метаболизирующихся другим изоферментом системы цитохром Р450 - фенитоина, теофиллина и вальпроевой кислоты. При одновременном назначении вышеуказанных препаратов требуется мониторирование их концентрации в плазме крови и ЭКГ. Кларитромицин может уменьшать клиренс триазолама и, таким образом, повышать его фармакологические эффекты с развитием сонливости и спутанности сознания. Для бензодиазепинов, выведение которых не зависит от изоферментов CYP3A4 (темазепам, нитразепам, лоразепам), клинически значимое взаимодействие с кларитромицином маловероятно. Имеются сообщения о повышении концентрации дигоксина в плазме крови пациентов, получавших одновременно дигоксин и кларитромицин. Следует постоянно контролировать содержание дигоксина в плазме крови, чтобы избежать дигиталисной интоксикации и развития потенциально летальных аритмий. Совместное применение с эрготамином и дигидроэрготамином (производные спорыньи) может привести к острой эрготаминовой интоксикации, проявляющейся тяжелым периферическим вазоспазмом, ишемией конечностей и других тканей, включая центральную нервную систему, и извращенной чувствительностью. При одновременном приеме кларитромицина с ингибиторами ГМГ-КоА-редуктазы - ловастатина и симвастатина - описаны редкие случаи рабдомиолиза. Эфавиренз, невирапин, рифампицин, рифабутин и рифапентин (индукторы цитохрома Р450) снижают концентрацию кларитромицина в плазме крови и ослабляют его терапевтический эффект, и вместе с тем повышают концентрацию 14(R)-гидроксикларитромицина. При совместном приеме флуконазола в дозе 200 мг и кларитромицина в дозе 1 г/сутки возможно увеличение равновесной концентрации и AUC кларитромицина на 33 % и 18 %, соответственно. Коррекции дозы кларитромицина не требуется. Необходимо обратить внимание на возможность перекрестной устойчивости между кларитромицином и другими антибиотиками из группы макролидов, а также линкомицином и клиндамицином. Одновременный прием кларитромицина и зидовудина у взрослых ВИЧ-инфицированных пациентов может привести к снижению равновесного уровня концентрации зидовудина. Необходим подбор доз кларитромицина и зидовудина. При одновременном назначении кларитромицина и ритонавира, атазанавира или других ингибиторов протеаз, возрастают значения плазменной концентрации как кларитромицина, который в таком случае не следует назначать в доза свыше 1 г/сутки, так и ингибитора протеаз. При совместном приеме кларитромицина и итраконазола возможно обоюдное повышение концентрации препаратов в плазме крови. За пациентами, одновременно принимающими итраконазол и кларитромицин, необходимо тщательное наблюдение из-за возможного усиления или удлинения фармакологических эффектов этих лекарственных средств. При одновременном приеме кларитромицина (1 г/сутки) и саквинавира (в мягких желатиновых капсулах, 1200 мг 3 раза в день) возможно увеличение AUC и равновесной концентрации саквинавира на 177 % и 187 %, соответственно, а кларитромицина на 40 %. При совместном назначении этих двух лекарственных средств в течение ограниченного времени в дозах/лекарственных формах, указанных выше, коррекции дозы не требуется. Поскольку при совместном назначении колхицина, который является субстратом для CYP3A и Р-гликопротеина, и кларитромицина, как и других макролидов - ингибиторов CYP3A и Р-гликопротеина, ингибирование может привести к усилению действия колхицина, пациентов следует тщательно наблюдать с целью выявления симптомов токсического действия колхицина. При применении кларитромицина с толтеродином у пациентов с низкой активностью изофермента CYP2D6 может потребоваться снижение дозы толтеродина в присутствии кларитромицина (ингибитор изоферментов CYP3A). При совместном приеме кларитромицина с верапамилом возможно снижение артериального давления, брадиаритмия и молочнокислый ацидоз. При использовании этравирина концентрация кларитромицина снижается, но повышается концентрация активного метаболита 14(R)-гидроксикларитромицина. При совместном применении кларитромицина и пероральных гипогликемических средств и/или инсулина может наблюдаться выраженная гипогликемия. На фоне одновременного приема кларитромицина и некоторых препаратов, снижающих концентрацию глюкозы, таких как натеглинид, пиоглитазон, репаглинид и росиглитазон, может иметь место ингибирование изофермента CYP3A кларитромицином, результатом чего может стать гипогликемия. Рекомендуется тщательный контроль концентрации глюкозы.
Амоксициллин
Антациды, глюкозамин, слабительные средства, аминогликозиды, пища замедляют и снижают абсорбцию амоксициллина; аскорбиновая кислота повышает абсорбцию. Пробенецид снижает выведение амоксициллина почками и увеличивает концентрацию амоксициллина в желчи и плазме крови. Бактерицидные антибиотики (в том числе аминогликозиды, цефалоспорины, ванкомицин, рифампицин) - синергическое действие; бактериостатические препараты (макролиды, хлорамфинекол, линкозамиды, тетрациклины, сульфаниламиды) - антагонистическое. При приеме амоксициллина в сочетании с метронидазолом наблюдается тошнота, рвота, анорексия, диарея, запор, боли в эпигастрии, расстройства пищеварения, в редких случаях желтуха, интерстициальный нефрит, нарушения гемопоэза. Амоксициллин повышает эффективность непрямых антикоагулянтов (подавляя кишечную микрофлору, снижает синтез витамина К и протромбиновый индекс), что приводит к удлинению времени свертывания крови. При необходимости корректируют дозу непрямых антикоагулянтов. Одновременное применение амоксициллина и аллопуринола повышает риск развития кожной сыпи. Амоксициллин уменьшает клиренс и повышает токсичность метотрексата, вероятно, из-за конкурентного ингибирования канальцевой почечной секреции метотрексата амоксициллином. У пациентов, получающих одновременно амоксициллин и метотрексат, следует тщательно контролировать плазменные концентрации последнего. Возможно увеличение времени абсорбции дигоксина на фоне терапии амоксициллином. При необходимости проводят корректировку дозы дигоксина. Диуретики, аллопуринол, оксифенбутазон, фенилбутазон, нестероидные противовоспалительные препараты и другие лекарственные средства, блокирующие канальцевую секрецию, повышают концентрацию амоксициллина в плазме крови. Амоксициллин снижает концентрацию эстрогенов и прогестеронов в плазме крови, что может привести к потере контрацептивного эффекта пероральных контрацептивов. Во время лечения амоксициллином следует использовать дополнительные негормональные методы контрацепции.
Лансопразол
Лансопразол замедляет элиминацию лекарственных средств, метаболизирующихся в печени путем микросомального окисления (в том числе диазепама, фенитоина, непрямых антикоагулянтов). Снижает на 10 % клиренс теофиллина. Замедляет рН-зависимую абсорбцию лекарственных средств, относящихся к группам слабых кислот, и ускоряет абсорбцию лекарственных средств, относящихся к группам оснований. Препятствует всасыванию кетоконазола, итраконазола, ампициллина, солей железа, дигоксина. Лансопразол замедляет всасывание цианокобаламина. Совместим с ибупрофеном, индометацином, диазепамом, пропранололом, варфарином, пероральными контрацептивами, фенитоином, преднизолоном. Сукральфат снижает биодоступность лансопразола на 30 %, поэтому необходимо соблюдать интервал между приемом этих лекарственных средств 30-40 мин. Антациды следует назначать за 1 час до или через 1-2 часа после приема лансопразола, так как они замедляют и снижают его абсорбцию. У добровольцев, одновременно получавших 60 мг лансопразола и 400 мг атазанавира в день, отмечалось снижение на 90 % AUC и Cmax последнего. Лансопразол не следует назначать одновременно с атазанавиром. Ритонавир (субстрат и ингибитор CYP2C19) может вариабельно повлиять на AUC лансопразола (увеличить или уменьшить). При необходимости сопутствующей терапии рекомендуется контроль терапевтических и возможных побочных эффектов, а также коррекция дозы лансопразола. Одновременный прием лансопразола и такролимуса (субстрат изофермента CYP3A4 и Р-гликопротеина) приводит к увеличению плазменной концентрации последнего (до 81 %). Следует проводить мониторинг концентрации такролимуса в плазме крови при одновременном назначении с лансопразолом. Одновременный прием флувоксамина (ингибитор изофермента CYP2C19) и лансопразола приводит к четырехкратному увеличению концентрации последнего в плазме крови. Рифампицин и зверобой продырявленный (индуцируют изоферменты CYP2C19 и CYP3A4) могут значительно снижать плазменные концентрации лансопразола.
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Противопоказан совместный прием с астемизолом, цизапридом, пимозидом, терфенадином, эрготамином и другими алкалоидами спорыньи, алпразоламом, мидазоламом, триазоламом.\u003cbr /\u003eС осторожностью назначают с карбамазепином, цилостазолом, циклоспорином, дизопирамидом, ловастатином, метилпреднизолоном, омепразолом, непрямыми антикоагулянтами (в том числе варфарином), хинидином, рифабутином, силденафилом, симвастатином, такролимусом, винбластином, фенитоином, теофиллином и вальпроевой кислотой (метаболизируются через другие изоферменты цитохрома Р450). Необходима коррекция дозы лекарственных средств и контроль концентрации в плазме крови.\u003cbr /\u003eПри совместном применении с цизапридом, пимозидом, терфенадином и астемизолом возможно увеличение концентрации последних в плазме крови, удлинение интервала QTи развитие сердечных аритмий, включая желудочковую пароксизмальную тахикардию, фибрилляцию, трепетание или мерцание желудочков, полиморфную желудочковую тахикардию по типу «пируэт» (см. раздел «Противопоказания»). Подобный механизм взаимодействия отмечается при применении лекарственных препаратов, метаболизирующихся другим изоферментом системы цитохром Р450 - фенитоина, теофиллина и вальпроевой кислоты. При одновременном назначении вышеуказанных препаратов требуется мониторирование их концентрации в плазме крови и ЭКГ.\u003cbr /\u003eКларитромицин может уменьшать клиренс триазолама и, таким образом, повышать его фармакологические эффекты с развитием сонливости и спутанности сознания.\u003cbr /\u003eДля бензодиазепинов, выведение которых не зависит от изоферментов CYP3A4 (темазепам, нитразепам, лоразепам), клинически значимое взаимодействие с кларитромицином маловероятно.\u003cbr /\u003eИмеются сообщения о повышении концентрации дигоксина в плазме крови пациентов, получавших одновременно дигоксин и кларитромицин. Следует постоянно контролировать содержание дигоксина в плазме крови, чтобы избежать дигиталисной интоксикации и развития потенциально летальных аритмий.\u003cbr /\u003eСовместное применение с эрготамином и дигидроэрготамином (производные спорыньи) может привести к острой эрготаминовой интоксикации, проявляющейся тяжелым периферическим вазоспазмом, ишемией конечностей и других тканей, включая центральную нервную систему, и извращенной чувствительностью.\u003cbr /\u003eПри одновременном приеме кларитромицина с ингибиторами ГМГ-КоА-редуктазы - ловастатина и симвастатина - описаны редкие случаи рабдомиолиза.\u003cbr /\u003eЭфавиренз, невирапин, рифампицин, рифабутин и рифапентин (индукторы цитохрома Р450) снижают концентрацию кларитромицина в плазме крови и ослабляют его терапевтический эффект, и вместе с тем повышают концентрацию 14(R)-гидроксикларитромицина.\u003cbr /\u003eПри совместном приеме флуконазола в дозе 200 мг и кларитромицина в дозе 1 г/сутки возможно увеличение равновесной концентрации и AUC кларитромицина на 33 % и 18 %, соответственно. Коррекции дозы кларитромицина не требуется.\u003cbr /\u003eНеобходимо обратить внимание на возможность перекрестной устойчивости между кларитромицином и другими антибиотиками из группы макролидов, а также линкомицином и клиндамицином.\u003cbr /\u003eОдновременный прием кларитромицина и зидовудина у взрослых ВИЧ-инфицированных пациентов может привести к снижению равновесного уровня концентрации зидовудина. Необходим подбор доз кларитромицина и зидовудина.\u003cbr /\u003eПри одновременном назначении кларитромицина и ритонавира, атазанавира или других ингибиторов протеаз, возрастают значения плазменной концентрации как кларитромицина, который в таком случае не следует назначать в доза свыше 1 г/сутки, так и ингибитора протеаз.\u003cbr /\u003eПри совместном приеме кларитромицина и итраконазола возможно обоюдное повышение концентрации препаратов в плазме крови. За пациентами, одновременно принимающими итраконазол и кларитромицин, необходимо тщательное наблюдение из-за возможного усиления или удлинения фармакологических эффектов этих лекарственных средств.\u003cbr /\u003eПри одновременном приеме кларитромицина (1 г/сутки) и саквинавира (в мягких желатиновых капсулах, 1200 мг 3 раза в день) возможно увеличение AUC и равновесной концентрации саквинавира на 177 % и 187 %, соответственно, а кларитромицина на 40 %. При совместном назначении этих двух лекарственных средств в течение ограниченного времени в дозах/лекарственных формах, указанных выше, коррекции дозы не требуется. Поскольку при совместном назначении колхицина, который является субстратом для CYP3A и Р-гликопротеина, и кларитромицина, как и других макролидов - ингибиторов CYP3A и Р-гликопротеина, ингибирование может привести к усилению действия колхицина, пациентов следует тщательно наблюдать с целью выявления симптомов токсического действия колхицина. При применении кларитромицина с толтеродином у пациентов с низкой активностью изофермента CYP2D6 может потребоваться снижение дозы толтеродина в присутствии кларитромицина (ингибитор изоферментов CYP3A).\u003cbr /\u003eПри совместном приеме кларитромицина с верапамилом возможно снижение артериального давления, брадиаритмия и молочнокислый ацидоз.\u003cbr /\u003eПри использовании этравирина концентрация кларитромицина снижается, но повышается концентрация активного метаболита 14(R)-гидроксикларитромицина.\u003cbr /\u003eПри совместном применении кларитромицина и пероральных гипогликемических средств и/или инсулина может наблюдаться выраженная гипогликемия. На фоне одновременного приема кларитромицина и некоторых препаратов, снижающих концентрацию глюкозы, таких как натеглинид, пиоглитазон, репаглинид и росиглитазон, может иметь место ингибирование изофермента CYP3A кларитромицином, результатом чего может стать гипогликемия. Рекомендуется тщательный контроль концентрации глюкозы. "}}]},{"id":3,"name":"Амоксициллин","slug":"amoksitsillin","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Антациды, глюкозамин, слабительные средства, аминогликозиды, пища замедляют и снижают абсорбцию амоксициллина; аскорбиновая кислота повышает абсорбцию.\u003cbr /\u003eПробенецид снижает выведение амоксициллина почками и увеличивает концентрацию амоксициллина в желчи и плазме крови. Бактерицидные антибиотики (в том числе аминогликозиды, цефалоспорины, ванкомицин, рифампицин) - синергическое действие; бактериостатические препараты (макролиды, хлорамфинекол, линкозамиды, тетрациклины, сульфаниламиды) - антагонистическое.\u003cbr /\u003eПри приеме амоксициллина в сочетании с метронидазолом наблюдается тошнота, рвота, анорексия, диарея, запор, боли в эпигастрии, расстройства пищеварения, в редких случаях желтуха, интерстициальный нефрит, нарушения гемопоэза.\u003cbr /\u003eАмоксициллин повышает эффективность непрямых антикоагулянтов (подавляя кишечную микрофлору, снижает синтез витамина К и протромбиновый индекс), что приводит к удлинению времени свертывания крови. При необходимости корректируют дозу непрямых антикоагулянтов. Одновременное применение амоксициллина и аллопуринола повышает риск развития кожной сыпи.\u003cbr /\u003eАмоксициллин уменьшает клиренс и повышает токсичность метотрексата, вероятно, из-за конкурентного ингибирования канальцевой почечной секреции метотрексата амоксициллином. У пациентов, получающих одновременно амоксициллин и метотрексат, следует тщательно контролировать плазменные концентрации последнего. Возможно увеличение времени абсорбции дигоксина на фоне терапии амоксициллином. При необходимости проводят корректировку дозы дигоксина.\u003cbr /\u003eДиуретики, аллопуринол, оксифенбутазон, фенилбутазон, нестероидные противовоспалительные препараты и другие лекарственные средства, блокирующие канальцевую секрецию, повышают концентрацию амоксициллина в плазме крови.\u003cbr /\u003eАмоксициллин снижает концентрацию эстрогенов и прогестеронов в плазме крови, что может привести к потере контрацептивного эффекта пероральных контрацептивов. Во время лечения амоксициллином следует использовать дополнительные негормональные методы контрацепции. "}}]},{"id":4,"name":"Лансопразол","slug":"lansoprazol","displayInMenu":true,"body":[{"type":"paragraph","data":{"text":"Лансопразол замедляет элиминацию лекарственных средств, метаболизирующихся в печени путем микросомального окисления (в том числе диазепама, фенитоина, непрямых антикоагулянтов). \u003cbr /\u003eСнижает на 10 % клиренс теофиллина.\u003cbr /\u003eЗамедляет рН-зависимую абсорбцию лекарственных средств, относящихся к группам слабых кислот, и ускоряет абсорбцию лекарственных средств, относящихся к группам оснований.\u003cbr /\u003eПрепятствует всасыванию кетоконазола, итраконазола, ампициллина, солей железа, дигоксина.\u003cbr /\u003eЛансопразол замедляет всасывание цианокобаламина.\u003cbr /\u003eСовместим с ибупрофеном, индометацином, диазепамом, пропранололом, варфарином, пероральными контрацептивами, фенитоином, преднизолоном. 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