Abilify Mycite

0

Abilify Mycite

الاسم العام: aripiprazole
الشكل الصيدلاني: قرص

على هذه الصفحة
  • تحذير محاصر
  • المؤشرات والاستخدام
  • الجرعة والإدارة
  • الجرعات ونقاط القوة
  • موانع الاستعمال
  • المحاذير والإحتياطات
  • ردود الفعل السلبية / الآثار الجانبية
  • تفاعل الأدوية
  • استخدم في مجموعات سكانية معينة
  • تعاطي المخدرات والاعتماد عليها
  • جرعة مفرطة
  • وصف
  • علم الصيدلة السريرية
  • علم السموم غير السريري
  • الدراسات السريرية
  • كيفية التزويد / التخزين والتداول
  • معلومات إرشاد المرضى

وسعت

تحذير: زيادة معدل الوفيات لدى المرضى المسنين المصابين بالاضطراب النفسي المرتبط بالخرف والأفكار والسلوكيات الانتحارية

زيادة معدل الوفيات لدى المرضى المسنين المصابين بالذهان المرتبط بالخرف

المرضى المسنون الذين يعانون من الذهان المرتبط بالخرف الذين يعالجون بالعقاقير المضادة للذهان هم في خطر متزايد من الموت. Abilify Mycite غير معتمد لعلاج المرضى الذين يعانون من الذهان المرتبط بالخرف [see Warnings and Precautions (5.1)] .

الأفكار والسلوكيات الانتحارية

زادت مضادات الاكتئاب من خطر الأفكار والسلوكيات الانتحارية لدى الأطفال والمرضى البالغين في الدراسات قصيرة المدى. راقب عن كثب جميع المرضى الذين عولجوا بمضادات الاكتئاب للتدهور السريري ، ولظهور الأفكار والسلوكيات الانتحارية [see Warnings and Precautions (5.2)]. لم تثبت سلامة وفعالية Abilify Mycite في مرضى الأطفال [see Use in Specific Populations (8.4)] .

مؤشرات واستخدام Abilify Mycite

يشار إلى Abilify Mycite ، وهو منتج تركيبة جهاز دوائي يتكون من أقراص aripiprazole المضمنة مع مستشعر حدث قابل للكشف (IEM) يهدف إلى تتبع ابتلاع المخدرات ، من أجل:

  • علاج البالغين المصابين بالفصام [see Clinical Studies (14.1)]
  • علاج الاضطراب ثنائي القطب من النوع الأول
    • العلاج الحاد للبالغين المصابين بنوبات الهوس والمختلطة كعلاج وحيد ومساعد لليثيوم أو فالبروات [see Clinical Studies (14.2)]
    • علاج للبالغين كعلاج وحيد وكمساعد لليثيوم أو فالبروات [see Clinical Studies (14.2)]
  • العلاج المساعد للبالغين الذين يعانون من اضطراب اكتئابي كبير [see Clinical Studies (14.3)]

حدود الاستخدام:

  • لم يتم تحديد قدرة Abilify Mycite على تحسين امتثال المريض أو تعديل جرعة aripiprazole [see Dosage and Administration (2.1)] .
  • لا ينصح باستخدام Abilify Mycite لتتبع ابتلاع المخدرات في “الوقت الحقيقي” أو أثناء الطوارئ لأن الكشف قد يتأخر أو لا يحدث [see Dosage and Administration (2.1)] .

Abilify Mycite الجرعة والإدارة

نظرة عامة على نظام Abilify Mycite

يتكون نظام Abilify Mycite من المكونات التالية:

  • قرص Aripiprazole مضمن بجهاز استشعار IEM (Abilify Mycite) ؛
  • التصحيح MYCITE ® (مستشعر يمكن ارتداؤه) الذي يكتشف الإشارة من مستشعر IEM بعد الابتلاع وينقل البيانات إلى هاتف ذكي ؛
  • MYCITE APP – تطبيق (تطبيق) للهواتف الذكية يستخدم مع هاتف ذكي متوافق لعرض معلومات للمريض ؛
  • بوابة على شبكة الإنترنت لمتخصصي الرعاية الصحية ومقدمي الرعاية

قبل الاستخدام الأولي للمريض لنظام Abilify Mycite System ، يسهل استخدام المنتج المركب ومكوناته (التصحيح ، التطبيق ، البوابة الإلكترونية) والتأكد من أن المريض قادر على استخدام الهواتف الذكية والتطبيقات وراغبًا فيها. قبل استخدام أي مكون من مكونات نظام Abilify Mycite ، يجب توجيه المرضى إلى:

  • قم بتنزيل تطبيق MYCITE واتبع جميع تعليمات الاستخدام.
  • تأكد من أن التطبيق متوافق مع هواتفهم الذكية المحددة.

على الرغم من أنه سيتم اكتشاف معظم عمليات الاستيعاب خلال 30 دقيقة ، فقد يستغرق تطبيق الهاتف الذكي وبوابة الويب ما يصل إلى ساعتين لاكتشاف ابتلاع Abilify Mycite ؛ في بعض الحالات ، قد لا يتم اكتشاف ابتلاع الجهاز اللوحي. إذا لم يتم اكتشاف الجهاز اللوحي بعد الابتلاع ، فلا تكرر الجرعة [see Adverse Reactions (6)] .

تتم الإشارة إلى حالة تصحيح MYCITE من خلال رمز الحالة في التطبيق لإبلاغ المستخدم بأن التصحيح ملتزم بشكل صحيح ويعمل بشكل كامل. إرشاد المرضى للتأكد من إقران التطبيق مع التصحيح قبل الاستخدام. ارجع إلى المعلومات الواردة في عبوة المنتج والتعليمات الإلكترونية للاستخدام داخل تطبيق MYCITE.

تعليمات الإدارة

Abilify Mycite

إدارة Abilify Mycite شفويا مع أو بدون طعام [see Clinical Pharmacology (12.3)] . أقراص ابتلاع كاملة. لا تقسم أو تسحق أو تمضغ.

التصحيح MYCITE

قم بتطبيق التصحيح MYCITE فقط عندما يطلب منك التطبيق على الجانب الأيسر من الجسم فوق الحافة السفلية من القفص الصدري. لا تضع لاصقة MYCITE في المناطق التي يتم فيها كشط الجلد أو تشققه أو التهابه أو تهيجه أو في مكان يتداخل مع منطقة الرقعة التي تمت إزالتها مؤخرًا. إرشاد المرضى للحفاظ على الرقعة عند الاستحمام أو السباحة أو ممارسة الرياضة. يجب تغيير التصحيح MYCITE أسبوعيا أو عاجلا حسب الحاجة. سيطلب التطبيق من المريض تغيير التصحيح وسيوجه المريض لتطبيق وإزالة التصحيح بشكل صحيح. يحتاج المرضى الذين يخضعون للتصوير بالرنين المغناطيسي إلى إزالة الرقعة واستبدالها بواحد جديد في أقرب وقت ممكن. إذا كان هناك تهيج في الجلد ، فاطلب من المرضى إزالة اللصقة.

جرعة في الفصام

جرعة البدء والهدف الموصى بها لـ Abilify Mycite عند البالغين المصابين بالفصام هي 10 أو 15 مجم يوميًا. بشكل عام ، يجب عدم زيادة الجرعة قبل أسبوعين [see Clinical Pharmacology (12.3)] . الجرعة القصوى الموصى بها هي 30 ملغ يوميا ؛ ومع ذلك ، فإن الجرعات التي تزيد عن 15 مجم يوميًا لم تظهر أي فائدة إضافية ذات مغزى سريريًا.

الجرعة في اضطراب ثنائي القطب الأول

جرعة البدء الموصى بها في البالغين الذين يعانون من نوبات حادة ومختلطة مرتبطة بالاضطراب ثنائي القطب I هي 15 مجم تعطى مرة واحدة يوميًا كعلاج وحيد و 10 مجم إلى 15 مجم تعطى مرة واحدة يوميًا كعلاج مساعد مع الليثيوم أو الفالبروات. الجرعة المستهدفة الموصى بها من Abilify Mycite هي 15 مجم يوميًا ، كعلاج أحادي أو كعلاج مساعد مع الليثيوم أو الفالبروات. يمكن زيادة الجرعة إلى 30 ملغ يومياً بناءً على الاستجابة السريرية. الجرعة اليومية القصوى الموصى بها هي 30 ملغ.

الجرعة في العلاج المساعد لاضطراب الاكتئاب

جرعة البدء الموصى بها لـ Abilify Mycite كعلاج مساعد للبالغين الذين يعانون من MDD الذين يتناولون مضادات الاكتئاب هي 2 إلى 5 مجم يوميًا. نطاق الجرعة الموصى به هو 2 إلى 15 ملغ يوميا. يجب أن تحدث تعديلات الجرعة حتى 5 ملغ يوميًا بشكل تدريجي ، على فترات لا تقل عن أسبوع واحد. الجرعة اليومية القصوى الموصى بها هي 15 ملغ. إعادة التقييم بشكل دوري لتحديد استمرار الحاجة إلى علاج الصيانة.

تعديلات الجرعة لاعتبارات السيتوكروم P450

يوصى بتعديل الجرعة في المرضى المعروفين بالمستقلبات الضعيفة CYP2D6 وفي المرضى الذين يتناولون مثبطات CYP3A4 المصاحبة أو مثبطات CYP2D6 أو محفزات CYP3A4 القوية (انظر الجدول 1). عندما يتم سحب الدواء الذي يتم تناوله معًا من العلاج المركب ، يجب تعديل جرعة Abilify Mycite إلى مستواها الأصلي. عندما يتم سحب محفز CYP3A4 المُدار بشكل مشترك ، يجب تقليل جرعة Abilify Mycite إلى المستوى الأصلي على مدى أسبوع إلى أسبوعين. المرضى الذين قد يتلقون مزيجًا من مثبطات قوية ومتوسطة وضعيفة لـ CYP3A4 و CYP2D6 (على سبيل المثال ، مثبط CYP3A4 قوي ومثبط CYP2D6 معتدل أو مثبط CYP3A4 معتدل مع مثبط CYP2D6 معتدل) ، يمكن تخفيض الجرعات إلى واحد – ربع (25٪) من الجرعة المعتادة مبدئيًا ثم يتم تعديلها بناءً على الاستجابة السريرية.

الجدول 1: تعديلات الجرعة Abilify Mycite في المرضى الذين يعرفون CYP2D6 الفقراء الأيض والمرضى الذين يتناولون مثبطات CYP2D6 المصاحبة ، و / 3 مثبطات 3A4 ، و / أو محفزات CYP3A4

العواملتعديلات الجرعة Abilify Mycite
المعروف CYP2D6 ضعف التمثيل الغذائيإعطاء نصف الجرعة الموصى بها
المعروف CYP2D6 ضعف التمثيل الغذائي أخذ مثبطات CYP3A4 المصاحبة القوية (على سبيل المثال ، إيتراكونازول ، كلاريثروميسين)إعطاء ربع الجرعة الموصى بها
CYP2D6 قوي (على سبيل المثال ، الكينيدين ، فلوكستين ، باروكستين) أو مثبطات CYP3A4 (على سبيل المثال ، إيتراكونازول ، كلاريثروميسين)إعطاء نصف الجرعة الموصى بها
مثبطات CYP2D6 و CYP3A4 القويةإعطاء ربع الجرعة الموصى بها
محفزات CYP3A4 القوية (على سبيل المثال ، كاربامازيبين ، ريفامبين)مضاعفة الجرعة على مدى أسبوع إلى أسبوعين

عند إعطاء Abilify Mycite المساعد للمرضى الذين يعانون من اضطراب اكتئابي كبير ، يجب إعطاء Abilify Mycite بدون تعديل الجرعة كما هو محدد في [Dosage and Administration (2.5) ].

الجرعات ونقاط القوة

Abilify Mycite (أقراص aripiprazole مع جهاز استشعار) متاح كما هو موضح في الجدول 2.

الجدول 2: Abilify Mycite العروض التقديمية

قوة الجهاز اللوحيلون / شكل الكمبيوتر اللوحيعلامات اللوحي
2 ملغأخضر باهت
مستطيل معدل
“DA-029” و “2”
5 ملغأزرق شاحب
مستطيل معدل
“DA-030” و “5”
10 ملغمن البيض إلى الوردي الباهت
مستطيل معدل
“DA-031” و “10”
15 ملغأصفر شاحب
مستدير
“DA-032” و “15”
20 ملغأبيض إلى أبيض مصفر شاحب
مستدير
“DA-033” و “20”
30 ملغمن البيض إلى الوردي الباهت
مستدير
“DA-034” و “30”

موانع الاستعمال

يمنع استخدام Abilify Mycite في المرضى الذين لديهم تاريخ من تفاعل فرط الحساسية للأريبيبرازول. تراوحت ردود الفعل بين الحكة / الشرى إلى الحساسية المفرطة [see Adverse Reactions (6.2)] .

المحاذير والإحتياطات

زيادة معدل الوفيات لدى المرضى المسنين المصابين بالذهان المرتبط بالخرف

المرضى المسنون الذين يعانون من الذهان المرتبط بالخرف الذين يعالجون بالأدوية المضادة للذهان هم في خطر متزايد للوفاة. كشفت تحليلات 17 تجربة محكومة بالعلاج الوهمي (مدة مشروطة لمدة 10 أسابيع) ، إلى حد كبير في المرضى الذين يتناولون الأدوية المضادة للذهان غير النمطية ، عن خطر الوفاة في المرضى الذين عولجوا بالعقاقير بين 1.6 إلى 1.7 مرة من خطر الوفاة في المرضى الذين عولجوا بالغفل. على مدار تجربة نموذجية مضبوطة لمدة 10 أسابيع ، كان معدل الوفيات في المرضى الذين عولجوا بالعقاقير حوالي 4.5 ٪ ، مقارنة بمعدل 2.6 ٪ في مجموعة الدواء الوهمي.

على الرغم من اختلاف أسباب الوفاة ، يبدو أن معظم الوفيات كانت إما أمراض القلب والأوعية الدموية (على سبيل المثال ، قصور القلب ، والوفاة المفاجئة) أو معدية (مثل الالتهاب الرئوي) في الطبيعة. تشير الدراسات القائمة على الملاحظة إلى أن العلاج بالأدوية المضادة للذهان التقليدية ، على غرار الأدوية المضادة للذهان غير التقليدية ، قد يزيد معدل الوفيات. إن المدى الذي يمكن أن تُعزى به نتائج زيادة معدل الوفيات في الدراسات القائمة على الملاحظة إلى العقار المضاد للذهان بدلاً من بعض خصائص (خصائص) المرضى غير واضحة. Abilify Mycite غير معتمد لعلاج المرضى الذين يعانون من الذهان المرتبط بالخرف [see Boxed Warning, and Warnings and Precautions (5.3)] .

الأفكار والسلوكيات الانتحارية لدى الأطفال والمرضى البالغين

في التحليلات المجمعة للتجارب التي تسيطر عليها وهمي للأدوية المضادة للاكتئاب (SSRIs وغيرها من فئات مضادات الاكتئاب) التي شملت ما يقرب من 77000 مريض بالغ وأكثر من 4،400 مريض من الأطفال ، كان معدل حدوث الأفكار والسلوكيات الانتحارية لدى الأطفال والمرضى البالغين أكبر في المرضى الذين عولجوا بمضادات الاكتئاب من المرضى الذين عولجوا بالغفل. لم تثبت سلامة وفعالية Abilify Mycite في مرضى الأطفال [see Use in Specific Populations (8.4)]. يتم تقديم الاختلافات بين الدواء الوهمي في عدد حالات الأفكار والسلوكيات الانتحارية لكل 1000 مريض تم علاجهم في الجدول 3.

لم تحدث حالات انتحار في أي من دراسات طب الأطفال. كانت هناك حالات انتحار في دراسات البالغين ، لكن العدد لم يكن كافيًا للتوصل إلى أي استنتاج حول تأثير الأدوية المضادة للاكتئاب على الانتحار.

الجدول 3: اختلافات الاختطار في عدد حالات التفكير أو السلوك الانتحاري في تجارب مضادات الاكتئاب التي تسيطر عليها وهمي مجمعة في المرضى الأطفال والبالغين

نطاق العمر (سنوات)اختلاف الدواء والعلاج الوهمي في عدد المرضى الذين يعانون من أفكار أو سلوكيات انتحارية لكل 1000 مريض تمت معالجتهم
الزيادات بالمقارنة مع الدواء الوهمي
<1814 مريضا إضافيا
18 إلى 245 مرضى إضافيين
انخفاض مقابل الدواء الوهمي
25 إلى 64مريض واحد أقل
≥656 مرضى أقل

من غير المعروف ما إذا كان خطر الأفكار والسلوكيات الانتحارية لدى الأطفال والمرضى البالغين يمتد إلى الاستخدام على المدى الطويل ، أي أكثر من أربعة أشهر. ومع ذلك ، هناك أدلة كبيرة من تجارب الصيانة التي تسيطر عليها وهمي لدى البالغين الذين يعانون من MDD أن مضادات الاكتئاب تؤخر تكرار الاكتئاب.

راقب جميع المرضى الذين عولجوا بمضادات الاكتئاب للتدهور السريري وظهور الأفكار والسلوكيات الانتحارية ، خاصة خلال الأشهر القليلة الأولى من العلاج بالعقاقير وفي أوقات تغيرات الجرعة. قم باستشارة أفراد الأسرة أو مقدمي الرعاية للمرضى لرصد التغييرات في السلوك ولتنبيه مقدم الرعاية الصحية. ضع في اعتبارك تغيير النظام العلاجي ، بما في ذلك ربما التوقف عن Abilify Mycite ، في المرضى الذين يكون اكتئابهم أسوأ باستمرار ، أو الذين يعانون من أفكار أو سلوكيات انتحارية طارئة.

ردود الفعل السلبية الدماغية الوعائية ، بما في ذلك السكتة الدماغية ، في المرضى المسنين الذين يعانون من الذهان المرتبط بالخرف

في الدراسات السريرية التي تسيطر عليها وهمي (اثنان من الجرعات المرنة ودراسة واحدة بجرعة ثابتة) من الذهان المرتبط بالخرف ، كان هناك زيادة في حدوث الأحداث الضائرة الوعائية الدماغية (على سبيل المثال ، السكتة الدماغية ، نوبة نقص تروية عابرة) ، بما في ذلك الوفيات ، في علاج أريبيبرازول المرضى (متوسط ​​العمر: 84 سنة ؛ النطاق: 78 إلى 88 سنة). في دراسة الجرعة الثابتة ، كانت هناك علاقة ذات دلالة إحصائية واستجابة للجرعة للأحداث الضائرة الوعائية الدماغية في المرضى الذين عولجوا بأريبيبرازول. Abilify Mycite غير معتمد لعلاج المرضى الذين يعانون من الذهان المرتبط بالخرف [see Boxed Warning] .

المتلازمة الخبيثة للذهان (NMS)

قد يُشار إلى أحد أعراض الأعراض المميتة في بعض الأحيان باسم المتلازمة الخبيثة للذهان (NMS) مع إعطاء الأدوية المضادة للذهان ، بما في ذلك Abilify Mycite. المظاهر السريرية لـ NMS هي فرط الحرارة ، وتصلب العضلات ، والحالة العقلية المتغيرة ، ودليل على عدم الاستقرار اللاإرادي (عدم انتظام النبض أو ضغط الدم ، عدم انتظام دقات القلب ، الحجاب الحاجز ، وخلل ضربات القلب). قد تشمل العلامات الإضافية ارتفاع فوسفوكيناز الكرياتين ، بيلة ميوغلوبينية (انحلال الربيدات) ، والفشل الكلوي الحاد.

التقييم التشخيصي للمرضى الذين يعانون من هذه المتلازمة معقد. عند الوصول إلى التشخيص ، من المهم استبعاد الحالات التي تتضمن فيها العروض السريرية مرضًا طبيًا خطيرًا (مثل الالتهاب الرئوي والعدوى الجهازية) وعلامات وأعراض خارج السبيل الهرمي غير المعالجة أو غير كافية (EPS). تشمل الاعتبارات الهامة الأخرى في التشخيص التفريقي السمية المركزية لمضادات الكولين ، والضربات الحرارية ، وحمى الدواء ، وأمراض الجهاز العصبي المركزي الأساسي.

يجب أن تتضمن إدارة NMS: 1) التوقف الفوري عن الأدوية المضادة للذهان والأدوية الأخرى غير الضرورية للعلاج المتزامن ؛ 2) علاج الأعراض المكثفة والمراقبة الطبية ؛ و 3) علاج أي مشاكل طبية خطيرة يصاحبها تتوفر علاجات محددة. لا يوجد اتفاق عام حول أنظمة علاج دوائية محددة ل NMS غير معقدة.

إذا كان المريض يحتاج إلى علاج بالعقاقير المضادة للذهان بعد الشفاء من NMS ، فيجب النظر بعناية في إعادة إدخال العلاج بالعقاقير. يجب مراقبة المريض بعناية ، حيث تم الإبلاغ عن تكرار NMS.

خلل الحركة المتأخر

قد تتطور متلازمة الحركات اللاإرادية واللاإرادية المحتملة في المرضى الذين يعالجون بالأدوية المضادة للذهان ، بما في ذلك Abilify Mycite. على الرغم من أن انتشار المتلازمة يبدو أنه أعلى بين كبار السن ، وخاصة النساء المسنات ، فمن المستحيل الاعتماد على تقديرات الانتشار للتنبؤ ، عند بدء العلاج بمضادات الذهان ، بالمرضى الذين من المحتمل أن يصابوا بالمتلازمة. ما إذا كانت منتجات الأدوية المضادة للذهان تختلف في قدرتها على التسبب في خلل الحركة المتأخر غير معروف.

يُعتقد أن خطر الإصابة بخلل الحركة المتأخر واحتمالية أن يصبح لا رجعة فيه يزداد مع زيادة مدة العلاج والجرعة التراكمية الإجمالية للأدوية المضادة للذهان التي يتم إعطاؤها للمريض. ومع ذلك ، يمكن أن تتطور المتلازمة ، على الرغم من أنها أقل شيوعًا ، بعد فترات علاج قصيرة نسبيًا بجرعات منخفضة.

قد تتحول المتلازمة ، جزئيًا أو كليًا ، إذا تم سحب العلاج المضاد للذهان. ومع ذلك ، فإن العلاج المضاد للذهان نفسه قد يقمع (أو يقمع جزئيًا) علامات وأعراض المتلازمة ، وبالتالي ، قد يخفي العملية الكامنة. إن تأثير قمع الأعراض على المسار الطويل للمتلازمة غير معروف.

بالنظر إلى هذه الاعتبارات ، يجب وصف Abilify Mycite بطريقة من المرجح أن تقلل من حدوث خلل الحركة المتأخر. بشكل عام ، يجب حجز العلاج بمضادات الذهان المزمنة للمرضى الذين يعانون من مرض مزمن (1) معروف باستجابته للأدوية المضادة للذهان و (2) الذين لا تتوفر لهم العلاجات البديلة الفعالة بنفس القدر ولكن الأقل خطورة. في المرضى الذين يحتاجون إلى علاج مزمن ، يجب البحث عن أصغر جرعة وأقصر مدة علاج تنتج استجابة سريرية مرضية. يجب إعادة تقييم الحاجة لاستمرار العلاج بشكل دوري.

إذا ظهرت علامات وأعراض خلل الحركة المتأخر في المريض على Abilify Mycite ، فيجب النظر في إيقاف الدواء. ومع ذلك ، قد يحتاج بعض المرضى إلى علاج Abilify Mycite على الرغم من وجود المتلازمة.

التغييرات الأيضية

تسببت الأدوية المضادة للذهان غير التقليدية في تغيرات التمثيل الغذائي التي تشمل ارتفاع السكر في الدم ، وداء السكري ، وعسر شحميات الدم ، وزيادة وزن الجسم. بينما ثبت أن جميع الأدوية في الصف تنتج بعض التغيرات الأيضية ، فإن كل دواء له ملف خطر خاص به.

فرط سكر الدم / داء السكري

تم الإبلاغ عن فرط سكر الدم ، في بعض الحالات الشديدة والمرتبطة بالحماض الكيتوني أو الغيبوبة المفرطة أو الموت ، في المرضى الذين عولجوا بمضادات الذهان غير التقليدية. كانت هناك تقارير عن فرط سكر الدم في المرضى الذين عولجوا بأريبيبرازول [see Adverse Reactions (6.1, 6.2)] . إن تقييم العلاقة بين استخدام مضادات الذهان غير التقليدية وتشوهات الجلوكوز معقدة بسبب احتمال زيادة خطر الإصابة بمرض السكري في الخلفية لدى مرضى الفصام وزيادة الإصابة بمرض السكري بين عامة السكان. بالنظر إلى هذه الإرباكات ، فإن العلاقة بين استخدام مضادات الذهان غير التقليدية والأحداث السلبية المرتبطة بسكر الدم غير مفهومة تمامًا. ومع ذلك ، تشير الدراسات الوبائية إلى زيادة خطر حدوث تفاعلات ضائرة ذات صلة بفرط سكر الدم لدى المرضى الذين يعالجون بمضادات الذهان غير التقليدية.

يجب مراقبة المرضى الذين لديهم تشخيص ثابت لمرض السكري الذين بدأوا في تناول مضادات الذهان غير التقليدية بانتظام لتفاقم السيطرة على الجلوكوز. يجب على المرضى الذين يعانون من عوامل خطر الإصابة بداء السكري (على سبيل المثال ، السمنة ، والتاريخ العائلي لمرض السكري) الذين يبدأون العلاج بمضادات الذهان غير التقليدية أن يخضعوا لاختبار سكر الدم الصائم في بداية العلاج وبشكل دوري أثناء العلاج. يجب مراقبة أي مريض يعالج بمضادات الذهان غير التقليدية لأعراض فرط سكر الدم بما في ذلك عطاش ، بوال ، عرق ، وضعف. يجب على المرضى الذين تظهر عليهم أعراض فرط سكر الدم أثناء العلاج بمضادات الذهان غير التقليدية الخضوع لاختبار سكر الدم الصائم. في بعض الحالات ، تم حل فرط سكر الدم عندما توقف مضادات الذهان غير التقليدية. ومع ذلك ، يحتاج بعض المرضى إلى استمرار العلاج من مرض السكري على الرغم من التوقف عن الدواء المضاد للذهان غير النمطي.

في تحليل 13 تجربة علاج أحادية مضبوطة بالغفل ، في المقام الأول مع الفصام أو الاضطراب ثنائي القطب ، لم يكن متوسط ​​التغيير في صوم الجلوكوز في المرضى الذين عولجوا في أريبيبرازول (+4.4 مجم / ديسيلتر ؛ متوسط ​​التعرض 25 يومًا ؛ N = 1057) بشكل ملحوظ يختلف عن المرضى الذين عولجوا بالغفل (+2.5 مجم / ديسيلتر ؛ متوسط ​​التعرض 22 يومًا ؛ N = 799). يوضح الجدول 4 نسبة المرضى الذين عولجوا بأريبيبرازول مع جلوكوز الصيام العادي والحدود عند خط الأساس (التعرض المتوسط ​​25 يومًا) الذين لديهم قياسات عالية للجلوكوز أثناء الصوم عالية العلاج مقارنة بالمرضى الذين عولجوا بالغفل (متوسط ​​التعرض 22 يومًا).

الجدول 4: التغيرات في جلوكوز الصيام في تجارب العلاج الأحادي التي تسيطر عليها وهمي في المرضى البالغين (الفصام في المقام الأول والاضطراب ثنائي القطب)

تغيير الفئة (مرة واحدة على الأقل) من خط الأساسذراع العلاجن / ن٪
السكر الصائمعادي إلى مرتفع
(<100 ملجم / دل إلى to126 ملجم / دل)
Aripiprazole31/8223.8
الوهمي22/6053.6
حد أعلى إلى أعلى
(≥100 ملجم / دل و <126 ملجم / دل إلى ≥126 ملجم / دل)
Aripiprazole31/17617.6
الوهمي13/1429.2

في 24 أسبوعًا ، لم يكن متوسط ​​التغيير في جلوكوز الصيام في المرضى الذين عولجوا بأريبيبرازول مختلفًا بشكل ملحوظ عن المرضى الذين عولجوا بالغفل [+2.2 mg/dL (n=42) and +9.6 mg/dL (n=28), respectively].

لم يكن التغيير في جلوكوز الصيام في المرضى الذين عولجوا بأريبيبرازول مع اضطراب اكتئابي كبير (+0.7 مجم / ديسيلتر ؛ متوسط ​​التعرض 42 يومًا ؛ N = 241) لم يكن مختلفًا بشكل ملحوظ عن المرضى الذين عولجوا بالغفل (+0.8 مجم / ديسيلتر ؛ متوسط التعرض 42 يومًا ؛ N = 246). يوضح الجدول 5 نسبة المرضى البالغين الذين يعانون من تغيرات في مستويات الجلوكوز أثناء الصيام من تجربتين مساعدتين يتم التحكم فيهما بالغفل (متوسط ​​التعرض 42 يومًا) في المرضى الذين يعانون من اضطراب اكتئابي كبير.

الجدول 5: التغيرات في جلوكوز الصيام من التجارب المساعدة التي تسيطر عليها وهمي في المرضى البالغين الذين يعانون من اضطراب اكتئابي كبير

تغيير الفئة (مرة واحدة على الأقل) من خط الأساسذراع العلاجن / ن٪
السكر الصائمعادي إلى مرتفع
(<100 ملجم / دل إلى to126 ملجم / دل)
Aripiprazole2/2011.0
الوهمي2/2041.0
حد أعلى إلى أعلى
(≥100 ملجم / دل و <126 ملجم / دل إلى ≥126 ملجم / دل)
Aripiprazole4/3411.8
الوهمي3/378.1

عسر شحميات الدم

وقد لوحظت تغيرات غير مرغوب فيها في الدهون في المرضى الذين عولجوا بمضادات الذهان غير التقليدية.

كانت التحليلات للمرضى الذين تعرضوا لمدة 12 أو 24 أسبوعًا على الأقل محدودة بسبب عدد صغير من المرضى. يوضح الجدول 6 نسبة المرضى البالغين ، بشكل رئيسي من الفصام المجمّع والاضطرابات ثنائية القطب التي تسيطر عليها العلاج الوهمي ، مع التغيرات في الكوليسترول الكلي (مجمعة من 17 تجربة ؛ التعرض المتوسط ​​21 إلى 25 يومًا) ، الدهون الثلاثية الصيام (مجمعة من ثماني تجارب ؛ متوسط التعرض 42 يومًا) ، الكولسترول الصائم LDL (مجمَّع من ثماني تجارب ؛ متوسط ​​التعرض 39 إلى 45 يومًا ، باستثناء المرضى الذين عولجوا بالغفل بقياسات LDL الصيامية العادية ، الذين تعرضوا للعلاج الوسيط لمدة 24 يومًا) والكوليسترول HDL (مجمَّع من تسعة المحاكمات ؛ التعرض المتوسط ​​40 إلى 42 يومًا).

الجدول 6: التغييرات في معلمات الدهون في الدم من التجارب العلاجية التي تسيطر عليها وهمي في البالغين (الفصام في المقام الأول والاضطراب ثنائي القطب)

ذراع العلاجن / ن٪

الكولسترول الكلي
عادي إلى مرتفع
(<200 ملجم / دل إلى ≥240 ملجم / دل)

Aripiprazole34/13572.5
الوهمي27/9732.8

الدهون الثلاثية
عادي إلى مرتفع
(<150 ملجم / دل إلى ≥200 ملجم / دل)

Aripiprazole40/5397.4
الوهمي30/4317.0

الصوم كوليسترول LDL
عادي إلى مرتفع
(<100 مجم / ديسيلتر إلى ≥160 مجم / ديسيلتر)

Aripiprazole2/3320.6
الوهمي2/2680.7

الكوليسترول الحميد
عادي الى منخفض
(≥40 مجم / ديسيلتر <40 مجم / ديسيلتر)

Aripiprazole121/106611.4
الوهمي99/79412.5

في تجارب العلاج الأحادي عند البالغين ، كانت نسبة المرضى عند 12 أسبوعًا و 24 أسبوعًا مع تغيرات من الطبيعي إلى المرتفع في الكوليسترول الكلي (الصيام / غير الصائم) ، وثلاثي الغليسريد ، وكوليسترول LDL الصيامي متشابهين بين المرضى المعالجين بالأريبيبرازول وهمي: في 12 أسبوعًا ، إجمالي الكوليسترول (الصيام / عدم الصيام) ، 1/71 (1.4٪) مقابل 3/74 (4.1٪) ؛ الدهون الثلاثية أثناء الصيام ، 8/62 (12.9٪) مقابل 5/37 (13.5٪) ؛ الصوم كوليسترول LDL ، 0/34 (0٪) مقابل 1/25 (4.0٪) ، على التوالي ؛ وفي 24 أسبوعًا ، إجمالي الكوليسترول (الصيام / عدم الصيام) ، 1/42 (2.4٪) مقابل 3/37 (8.1٪) ؛ الدهون الثلاثية أثناء الصيام ، 5/34 (14.7٪) مقابل 5/20 (25٪) ؛ الصوم كوليسترول LDL ، 0/22 (0٪) مقابل 1/18 (5.6٪) ، على التوالي.

يوضح الجدول 7 نسبة المرضى الذين يعانون من تغيرات في الكوليسترول الكلي (الصيام / غير الصائم) ، وثلاثي الغليسريد الصائم ، وكوليسترول LDL الصيامي ، والكوليسترول HDL من تجربتين مساعدتين يتم التحكم فيهما بالغفل في المرضى البالغين الذين يعانون من اضطراب اكتئابي كبير (التعرض المتوسط ​​42 يومًا).

الجدول 7: التغييرات في معلمات الدهون في الدم من التجارب المساعدة التي تسيطر عليها وهمي في المرضى البالغين الذين يعانون من اضطراب اكتئابي كبير

ذراع العلاجن / ن٪

الكولسترول الكلي
عادي إلى مرتفع
(<200 ملجم / دل إلى ≥240 ملجم / دل)

Aripiprazole3/1392.2
الوهمي7/1355.2

الدهون الثلاثية
عادي إلى مرتفع
(<150 ملجم / دل إلى ≥200 ملجم / دل)

Aripiprazole14/1459.7
الوهمي6/1474.1

الصوم كوليسترول LDL
عادي إلى مرتفع
(<100 مجم / ديسيلتر إلى ≥160 مجم / ديسيلتر)

Aripiprazole0/540
الوهمي0/730

الكوليسترول الحميد
عادي الى منخفض
(≥40 مجم / ديسيلتر <40 مجم / ديسيلتر)

Aripiprazole17/3185.3
الوهمي10/2863.5

زيادة الوزن

وقد لوحظ زيادة الوزن مع استخدام مضادات الذهان غير النمطية. يوصى بالمراقبة السريرية للوزن.

في تحليل 13 تجربة علاجية واحدة يتم التحكم فيها بالغفل ، بشكل رئيسي من الفصام المجمّع والاضطراب ثنائي القطب ، مع تعرض متوسط ​​يتراوح من 21 إلى 25 يومًا ، كان متوسط ​​التغيير في وزن الجسم لدى المرضى المعالجين بالأريبيبرازول +0.3 كجم (N = 1673) مقارنة إلى -0.1 كجم (N = 1100) في المرضى الذين تسيطر عليهم وهمي. في 24 أسبوعًا ، كان متوسط ​​التغيير من خط الأساس في وزن الجسم في المرضى الذين عولجوا بأريبيبرازول –1.5 كجم (n = 73) مقارنة بـ –0.2 كجم (n = 46) في المرضى الذين عولجوا بالغفل.

في التجارب التي تضيف أريبيبرازول إلى مضادات الاكتئاب ، تلقى المرضى أولاً 8 أسابيع من العلاج المضاد للاكتئاب متبوعًا بـ 6 أسابيع من أريبيبرازول المساعد أو الدواء الوهمي بالإضافة إلى العلاج المستمر المضاد للاكتئاب. بلغ متوسط ​​التغيير في وزن الجسم في المرضى الذين يتلقون أريبيبرازول مساعد +1.7 كجم (N = 347) مقارنة مع +0.4 كجم (N = 330) في المرضى الذين يتلقون علاجًا وهميًا مساعدًا.

يوضح الجدول 8 النسبة المئوية للمرضى البالغين الذين لديهم زيادة في الوزن ≥7٪ من وزن الجسم عن طريق الإشارة.

الجدول 8: النسبة المئوية للمرضى من تجارب مضبوطة بالغفل في المرضى البالغين الذين اكتسبوا وزنًا ≥7٪ من وزن الجسم

زيادة الوزن ≥7٪ من وزن الجسمدلالةذراع العلاجنالمرضى (٪)

*
4 إلى 6 أسابيع.

مدة 3 أسابيع.

6 أسابيع.

فصام *Aripiprazole85269 (8.1)
الوهمي37912 (3.2)
هوس ثنائي القطب †Aripiprazole71916 (2.2)
الوهمي59816 (2.7)
اضطراب اكتئابي رئيسي (علاج مساعد) ‡Aripiprazole34718 (5.2)
الوهمي3302 (0.6)

القمار المرضي والسلوكيات القهرية الأخرى

تشير تقارير حالة ما بعد التسويق إلى أن المرضى يمكن أن يواجهوا حوافز شديدة ، خاصة للمقامرة ، وعدم القدرة على التحكم في هذه الحوافز أثناء تناول الأريبيبرازول. الحوافز القهرية الأخرى ، التي يتم الإبلاغ عنها بشكل أقل تكرارًا ، تتضمن: الحوافز الجنسية ، والتسوق ، وتناول الطعام أو الأكل بنهم ، والسلوكيات الاندفاعية أو القهرية الأخرى. نظرًا لأن المرضى قد لا يتعرفون على هذه السلوكيات على أنها غير طبيعية ، فمن المهم أن يسأل الواصفون المرضى أو مقدمي الرعاية لهم على وجه التحديد عن تطوير حوافز المقامرة الجديدة أو الشديدة ، أو الحوافز الجنسية القهرية ، أو التسوق القهري ، أو الإفراط في تناول الطعام أو القهري ، أو الحوافز الأخرى أثناء العلاج مع Abilify Mycite. وتجدر الإشارة إلى أن أعراض التحكم في الاندفاع يمكن أن ترتبط بالاضطراب الأساسي. في بعض الحالات ، على الرغم من أنه ليس كل شيء ، تم الإبلاغ عن أن الحوافز قد توقفت عند تقليل الجرعة أو توقف الدواء. قد تؤدي السلوكيات القهرية إلى إلحاق الضرر بالمريض والآخرين إذا لم يتم التعرف عليه. فكر في تقليل الجرعة أو إيقاف الدواء إذا طور المريض مثل هذه الحوافز.

هبوط ضغط الدم الانتصابى

Abilify Mycite قد يسبب انخفاض ضغط الدم الانتصابي ، ربما بسبب عدائه مستقبلات الأدرينالية α 1. وقوع الأحداث المصاحبة لانخفاض ضغط الدم الانتصابي من التجارب قصيرة المدى التي تسيطر عليها وهمي للمرضى البالغين على أريبيبرازول عن طريق الفم (ن = 2467) شملت (حدوث أريبيبرازول ، وقوع وهمي) انخفاض ضغط الدم الانتصابي (1٪ ، 0.3٪) ، دوار الوضعي (0.5 ٪ و 0.3٪) و الإغماء (0.5٪ و 0.4٪) [see Adverse Reactions (6.1)].

لم يكن هناك اختلاف جوهري في حدوث أريبيبرازول عند حدوث تغير في معدل الانتظام في ضغط الدم (يعرف بانخفاض ضغط الدم الانقباضي ≥20 مم زئبقي مصحوبًا بزيادة في معدل ضربات القلب ≥25 نبضة في الدقيقة عند مقارنة قيم الاستلقاء) لأريبيبرازول. معدل حدوث الدواء الوهمي) لدى المرضى الذين عولجوا بأريبيبرازول عن طريق الفم (4٪ ، 2٪).

يجب استخدام Abilify Mycite بحذر في المرضى الذين يعانون من أمراض القلب والأوعية الدموية المعروفة (تاريخ احتشاء عضلة القلب أو أمراض القلب الإقفارية ، أو قصور القلب أو تشوهات التوصيل) ، أو أمراض الأوعية الدموية الدماغية ، أو الحالات التي قد تعرض المرضى لنقص ضغط الدم (الجفاف ونقص حجم الدم وعلاج ارتفاع ضغط الدم الأدوية) [see Drug Interactions (7.1)] .

السقوط

مضادات الذهان ، بما في ذلك Abilify Mycite ، قد تسبب النعاس ، انخفاض ضغط الدم الوضعي ، عدم الاستقرار الحركي والحسي ، مما قد يؤدي إلى السقوط ، وبالتالي الكسور أو الإصابات الأخرى. بالنسبة للمرضى الذين يعانون من أمراض أو حالات أو أدوية يمكن أن تؤدي إلى تفاقم هذه التأثيرات ، قم بإجراء تقييمات كاملة لمخاطر السقوط عند بدء العلاج بمضادات الذهان وبشكل متكرر للمرضى الذين يتلقون علاجًا طويل الأمد بمضادات الذهان.

قلة الكريات البيض ، قلة العدلات ، وندرة المحببات

في التجارب السريرية و / أو تجربة ما بعد التسويق ، تم الإبلاغ عن أحداث قلة الكريات البيض والعدلات المرتبطة مؤقتًا بالعوامل المضادة للذهان ، بما في ذلك أريبيبرازول. كما تم الإبلاغ عن ندرة المحببات.

تشمل عوامل الخطر المحتملة لقلة الكريات البيض / قلة العدلات انخفاض عدد خلايا الدم البيضاء الموجود مسبقًا (WBC) / عدد العدلات المطلق (ANC) وتاريخ نقص الكريات البيض الناجم عن المخدرات / قلة العدلات. في المرضى الذين لديهم تاريخ من انخفاض WBC / ANC الكبير سريريًا أو نقص الكريات البيض / قلة العدلات الناجم عن المخدرات ، قم بإجراء تعداد دم كامل (CBC) بشكل متكرر خلال الأشهر القليلة الأولى من العلاج. في مثل هؤلاء المرضى ، ضع في اعتبارك التوقف عن Abilify Mycite عند أول علامة على انخفاض كبير سريريًا في WBC في غياب عوامل مسببة أخرى.

راقب المرضى الذين يعانون من قلة العدلات المهمة سريريًا للحمى أو غيرها من الأعراض أو علامات العدوى وعلاجهم فورًا في حالة ظهور مثل هذه الأعراض أو العلامات. التوقف عن Abilify Mycite في المرضى الذين يعانون من قلة العدلات الشديدة (عدد العدلات المطلق <1000 / مم 3) واتبع تعدادات WBC الخاصة بهم حتى الشفاء.

النوبات

في تجارب قصيرة المدى مضبوطة بالغفل ، حدث المرضى الذين لديهم تاريخ من نوبات التشنجات / التشنجات المستبعدة في 0.1 ٪ (3/2467) من المرضى البالغين غير المشخصين الذين عولجوا بأريبيبرازول عن طريق الفم.

كما هو الحال مع الأدوية المضادة للذهان الأخرى ، يجب استخدام Abilify Mycite بحذر في المرضى الذين لديهم تاريخ من النوبات أو في الحالات التي تقلل من عتبة النوبة. قد تكون الظروف التي تخفض عتبة النوبة أكثر انتشارًا في السكان الذين يبلغون 65 عامًا أو أكثر.

إمكانية ضعف الإدراك والحركة

Abilify Mycite ، مثل مضادات الذهان الأخرى ، لديها القدرة على إضعاف الحكم أو التفكير أو المهارات الحركية. في تجارب قصيرة المدى مضبوطة بالغفل ، تم الإبلاغ عن النعاس (بما في ذلك التخدير) في 11٪ من المرضى المعالجين بأريبيبرازول مقارنة مع 6٪ من المرضى الذين عولجوا بالغفل. أدى النعاس (بما في ذلك التخدير) إلى التوقف في 0.3 ٪ (8/2467) من المرضى البالغين على أريبيبرازول عن طريق الفم في تجارب قصيرة المدى مضبوطة بالغفل.

يجب تحذير المرضى من تشغيل الآلات الخطرة ، بما في ذلك السيارات ، حتى يتأكدوا بشكل معقول من أن العلاج بـ Abilify Mycite لا يؤثر عليهم سلبًا.

تنظيم درجة حرارة الجسم

يعزى اختلال قدرة الجسم على خفض درجة حرارة الجسم الأساسية إلى العوامل المضادة للذهان. يُنصح بالعناية المناسبة عند وصف Abilify Mycite للمرضى الذين سيعانون من ظروف قد تساهم في ارتفاع درجة حرارة الجسم الأساسية (على سبيل المثال ، ممارسة التمارين الشديدة ، أو التعرض للحرارة الشديدة ، أو تلقي الأدوية المصاحبة لنشاط مضاد للكولين ، أو التعرض للجفاف).

عسر البلع

ارتبط عسر حركة المريء وتطلعاته باستخدام الأدوية المضادة للذهان ، بما في ذلك أريبيبرازول. يجب استخدام Abilify Mycite والأدوية المضادة للذهان الأخرى بحذر في المرضى المعرضين لخطر الالتهاب الرئوي التنفسي.

ردود الفعل السلبية

تمت مناقشة التفاعلات الضائرة التالية بمزيد من التفصيل في الأقسام الأخرى من الوسم:

  • زيادة معدل الوفيات لدى المرضى المسنين المصابين بالذهان المرتبط بالخرف [see Boxed Warning and Warnings and Precautions (5.1)]
  • الأفكار والسلوكيات الانتحارية لدى الأطفال والمرضى البالغين [see Boxed Warning and Warnings and Precautions (5.2)]
  • الأحداث الضائرة الوعائية الدماغية ، بما في ذلك السكتة الدماغية [see Warnings and Precautions (5.3)]
  • Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions (5.4)]
  • Tardive Dyskinesia [see Warnings and Precautions (5.5)]
  • Metabolic Changes [see Warnings and Precautions (5.6)]
  • Pathological Gambling and Other Compulsive Behaviors [see Warnings and Precautions (5.7)]
  • Orthostatic Hypotension [see Warnings and Precautions (5.8)]
  • Falls [see Warnings and Precautions (5.9)]
  • Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.10)]
  • Seizures [see Warnings and Precautions (5.11)]
  • Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.12)]
  • Body Temperature Regulation [see Warnings and Precautions (5.13)]
  • Dysphagia [see Warnings and Precautions (5.14)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Abilify Mycite for the treatment of adults with schizophrenia, treatment of adults with manic and mixed episodes associated with bipolar I disorder, and adjunctive treatment of adults with major depressive disorder (MDD) has been established and is based on trials of aripiprazole including 13,543 adult patients who participated in multiple-dose clinical trials in schizophrenia, bipolar disorder, major depressive disorder, and other disorders, and who had approximately 7619 patient-years of exposure to oral aripiprazole. A total of 3390 patients were treated with oral aripiprazole for at least 180 days and 1933 patients treated with oral aripiprazole had at least 1 year of exposure.

The conditions and duration of treatment with aripiprazole (monotherapy and adjunctive therapy with antidepressants or mood stabilizers) included (in overlapping categories) double-blind, comparative and noncomparative open-label studies, inpatient and outpatient studies, fixed- and flexible-dose studies, and short- and longer-term exposure.

The most common adverse reactions of aripiprazole in adult patients in clinical trials (≥10%) were nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia, and restlessness.

Adverse Reactions in Adult Patients with Schizophrenia

The following findings are based on a pool of five placebo-controlled trials (four 4-week and one 6-week) in which oral aripiprazole was administered in doses ranging from 2 to 30 mg/day.

The commonly observed adverse reaction associated with the use of aripiprazole tablets in patients with schizophrenia (incidence of 5% or greater and aripiprazole tablets incidence at least twice that for placebo) was akathisia (aripiprazole tablets 8%; placebo 4%).

Adverse Reactions in Adult Patients with Bipolar Mania

Adult Patients Who Received Monotherapy

The following findings are based on a pool of 3-week, placebo-controlled bipolar mania trials in which oral aripiprazole was administered at doses of 15 or 30 mg/day.

Commonly observed adverse reactions associated with the use of aripiprazole tablets in patients with bipolar mania (incidence of 5% or greater and aripiprazole tablets incidence at least twice that for placebo) are shown in Table 9.

Table 9: Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials of Adult Patients with Bipolar Mania Treated with Oral Aripiprazole Monotherapy

Percentage of Patients Reporting Reaction
Preferred TermAripiprazole tablets
(n=917)
Placebo
(n=753)
Akathisia134
Sedation83
Restlessness63
Tremor63
Extrapyramidal Disorder52

Table 10 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks in schizophrenia and up to 3 weeks in bipolar mania), including only those reactions that occurred in 2% or more of patients treated with aripiprazole tablets (doses ≥2 mg/day) and for which the incidence in patients treated with aripiprazole tablets was greater than the incidence in patients treated with placebo in the combined dataset.

Table 10: Adverse Reactions in Short-Term, Placebo-Controlled Trials in Adult Patients Treated with Oral Aripiprazole

Percentage of Patients Reporting Reaction *
System Organ Class
Preferred Term
Aripiprazole tablets
(n=1843)
Placebo
(n=1166)

*
Adverse reactions reported by at least 2% of patients treated with oral aripiprazole, except adverse reactions which had an incidence equal to or less than placebo

Eye Disorders
Blurred Vision31
Gastrointestinal Disorders
Nausea1511
Constipation117
Vomiting116
Dyspepsia97
Dry Mouth54
Toothache43
Abdominal Discomfort32
Stomach Discomfort32
General Disorders and Administration Site Conditions
Fatigue64
ألم32
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal Stiffness43
Pain in Extremity42
Myalgia21
Muscle Spasms21
Nervous System Disorders
Headache2723
Dizziness107
Akathisia104
Sedation74
Extrapyramidal Disorder53
Tremor53
Somnolence53
Psychiatric Disorders
Agitation1917
Insomnia1813
Anxiety1713
Restlessness53
Respiratory, Thoracic, and Mediastinal Disorders
Pharyngolaryngeal Pain32
Cough32

An examination of population subgroups did not reveal any clear evidence of differential adverse reaction incidence on the basis of age, gender, or race.

Adult Patients with Adjunctive Therapy with Bipolar Mania

The following findings are based on a placebo-controlled trial of adult patients with bipolar disorder in which aripiprazole tablets was administered at doses of 15 or 30 mg/day as adjunctive therapy with lithium or valproate.

In a study of patients who were already tolerating either lithium or valproate as monotherapy, discontinuation rates due to adverse reactions were 12% for patients treated with adjunctive aripiprazole tablets compared to 6% for patients treated with adjunctive placebo. The most common adverse drug reactions associated with discontinuation in the adjunctive aripiprazole-treated compared to placebo-treated patients were akathisia (5% and 1%, respectively) and tremor (2% and 1%, respectively).

The commonly observed adverse reactions associated with adjunctive aripiprazole tablets and lithium or valproate in patients with bipolar mania (incidence of 5% or greater and incidence at least twice that for adjunctive placebo) were: akathisia, insomnia, and extrapyramidal disorder.

Table 11 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute treatment (up to 6 weeks), including only those reactions that occurred in 2% or more of patients treated with adjunctive aripiprazole tablets (doses of 15 or 30 mg/day) and lithium or valproate and for which the incidence in patients treated with this combination was greater than the incidence in patients treated with placebo plus lithium or valproate.

Table 11: Adverse Reactions in a Short-Term, Placebo-Controlled Trial of Adjunctive Therapy in Patients with Bipolar Disorder

Percentage of Patients Reporting Reaction *
System Organ Class
Preferred Term
Aripiprazole tablets + Li or Val †
(n=253)
Placebo + Li or Val †
(n=130)

*
Adverse reactions reported by at least 2% of patients treated with oral aripiprazole, except adverse reactions which had an incidence equal to or less than placebo

Lithium or Valproate

Gastrointestinal Disorders
Nausea85
Vomiting40
Salivary Hypersecretion42
Dry Mouth21
Infections and Infestations
Nasopharyngitis32
Investigations
Weight Increased21
Nervous System Disorders
Akathisia195
Tremor96
Extrapyramidal Disorder51
Dizziness41
Sedation42
Psychiatric Disorders
Insomnia84
Anxiety41
Restlessness21

Adult Patients Receiving Aripiprazole Tablets as Adjunctive Treatment of Major Depressive Disorder

The following findings are based on a pool of two placebo-controlled trials of patients with major depressive disorder in which aripiprazole tablets were administered at doses of 2 mg to 20 mg as adjunctive treatment to continued antidepressant therapy.

The incidence of discontinuation due to adverse reactions was 6% for adjunctive aripiprazole-treated patients and 2% for adjunctive placebo-treated patients.

The commonly observed adverse reactions associated with the use of adjunctive aripiprazole tablets in patients with major depressive disorder (incidence of 5% or greater and aripiprazole tablets incidence at least twice that for placebo) were: akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision.

Table 12 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks), including only those adverse reactions that occurred in 2% or more of patients treated with adjunctive aripiprazole tablets (doses ≥2 mg/day) and for which the incidence in patients treated with adjunctive aripiprazole tablets was greater than the incidence in patients treated with adjunctive placebo in the combined dataset.

Table 12: Adverse Reactions in Short-Term, Placebo-Controlled Adjunctive Trials in Patients with Major Depressive Disorder

Percentage of Patients Reporting Reaction *
System Organ Class
Preferred Term
Aripiprazole tablets + ADT †
(n=371)
Placebo + ADT †
(n=366)

*
Adverse reactions reported by at least 2% of patients treated with adjunctive aripiprazole tablets, except adverse reactions which had an incidence equal to or less than placebo

Antidepressant Therapy

Eye Disorders
Blurred Vision61
Gastrointestinal Disorders
Constipation52
General Disorders and Administration Site Conditions
Fatigue84
Feeling Jittery31
Infections and Infestations
Upper Respiratory Tract Infection64
Investigations
Weight Increased32
Metabolism and Nutrition Disorders
Increased Appetite32
Musculoskeletal and Connective Tissue Disorders
Arthralgia43
Myalgia31
Nervous System Disorders
Akathisia254
Somnolence64
Tremor54
Sedation42
Dizziness42
Disturbance in Attention31
Extrapyramidal Disorder20
Psychiatric Disorders
Restlessness122
Insomnia82

Dose-Related Adverse Reactions in Patients with Schizophrenia

Dose response relationships for the incidence of treatment-emergent adverse events were evaluated from four trials in adult patients with schizophrenia comparing various fixed doses (2, 5, 10, 15, 20, and 30 mg/day) of oral aripiprazole to placebo. This analysis, stratified by study, indicated that the only adverse reaction to have a possible dose response relationship, and then most prominent only with 30 mg, was somnolence [including sedation]؛ (incidences were placebo, 7.1%; 10 mg, 8.5%; 15 mg, 8.7%; 20 mg, 7.5%; 30 mg, 12.6%).

Extrapyramidal Symptoms

Schizophrenia

In short-term, placebo-controlled trials in schizophrenia in adults, the incidence of reported EPS-related events, excluding events related to akathisia, for aripiprazole-treated patients was 13% vs. 12% for placebo; and the incidence of akathisia-related events for aripiprazole-treated patients was 8% vs. 4% for placebo.

Objectively collected data from those trials was collected on the Simpson Angus Rating Scale (for EPS), the Barnes Akathisia Scale (for akathisia), and the Assessments of Involuntary Movement Scales (for dyskinesias). In the adult schizophrenia trials, the objectively collected data did not show a difference between aripiprazole tablets and placebo, with the exception of the Barnes Akathisia Scale (aripiprazole tablets, 0.08; placebo, –0.05).

Similarly, in a long-term (26-week), placebo-controlled trial of schizophrenia in adults, objectively collected data on the Simpson Angus Rating Scale (for EPS), the Barnes Akathisia Scale (for akathisia), and the Assessments of Involuntary Movement Scales (for dyskinesias) did not show a difference between aripiprazole tablets and placebo.

Bipolar Mania

In the short-term, placebo-controlled trials in bipolar mania in adults, the incidence of reported EPS-related events, excluding events related to akathisia, for monotherapy aripiprazole-treated patients was 16% vs. 8% for placebo and the incidence of akathisia-related events for monotherapy aripiprazole-treated patients was 13% vs. 4% for placebo. In the 6-week placebo-controlled trial in bipolar mania for adjunctive therapy with lithium or valproate, the incidence of reported EPS-related events, excluding events related to akathisia for adjunctive aripiprazole-treated patients was 15% vs. 8% for adjunctive placebo and the incidence of akathisia-related events for adjunctive aripiprazole-treated patients was 19% vs. 5% for adjunctive placebo.

In the adult bipolar mania trials with monotherapy aripiprazole tablets, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between aripiprazole tablets and placebo (aripiprazole tablets, 0.50; placebo, –0.01 and aripiprazole tablets, 0.21; placebo, –0.05). Changes in the Assessments of Involuntary Movement Scales were similar for the aripiprazole tablets and placebo groups. In the bipolar mania trials with aripiprazole tablets as adjunctive therapy with either lithium or valproate, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between adjunctive aripiprazole tablets and adjunctive placebo (aripiprazole tablets, 0.73; placebo, 0.07 and aripiprazole tablets, 0.30; placebo, 0.11). Changes in the Assessments of Involuntary Movement Scales were similar for adjunctive aripiprazole tablets and adjunctive placebo.

Major Depressive Disorder

In the short-term, placebo-controlled trials in major depressive disorder, the incidence of reported EPS-related events, excluding events related to akathisia, for adjunctive aripiprazole-treated patients was 8% vs. 5% for adjunctive placebo-treated patients; and the incidence of akathisia-related events for adjunctive aripiprazole-treated patients was 25% vs. 4% for adjunctive placebo-treated patients.

In the major depressive disorder trials, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between adjunctive aripiprazole tablets and adjunctive placebo (aripiprazole tablets, 0.31; placebo, 0.03 and aripiprazole tablets, 0.22; placebo, 0.02). Changes in the Assessments of Involuntary Movement Scales were similar for the adjunctive aripiprazole tablets and adjunctive placebo groups.

Dystonia

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Skin Irritation for MYCITE Patch

Symptoms of skin irritation localized at the site of the MYCITE Patch may occur in some patients. In clinical studies, sixty-one patients (12.4%) experienced skin rashes localized at the site of patch placement.

Adverse Reactions in Long-Term, Double-Blind, Placebo-Controlled Trials

The adverse reactions reported in a 26-week, double-blind trial comparing oral aripiprazole and placebo in patients with schizophrenia were generally consistent with those reported in the short-term, placebo-controlled trials, except for a higher incidence of tremor [8% (12/153) for aripiprazole tablets vs. 2% (3/153) for placebo]. In this study, the majority of the cases of tremor were of mild intensity (8/12 mild and 4/12 moderate), occurred early in therapy (9/12 ≤49 days), and were of limited duration (7/12 ≤10 days). Tremor led to discontinuation (<1%) of aripiprazole tablets. In addition, in a long-term (52 weeks), active-controlled study, the incidence of tremor was 5% (40/859) for aripiprazole tablets. A similar profile was observed in a long-term monotherapy study and a long-term adjunctive study with lithium and valproate in bipolar disorder.

Other Adverse Reactions Observed during the Premarketing Evaluation of Aripiprazole

Other adverse reactions associated with aripiprazole are presented below. The listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.

Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients:

  • Blood and Lymphatic System Disorders: rare – thrombocytopenia

  • Cardiac Disorders: infrequent – bradycardia, palpitations, rare – atrial flutter, cardio-respiratory arrest, atrioventricular block, atrial fibrillation, angina pectoris, myocardial ischemia, myocardial infarction, cardiopulmonary failure

  • Eye Disorders: infrequent – photophobia; rare – diplopia

  • Gastrointestinal Disorders: infrequent – gastroesophageal reflux disease

  • General Disorders and Administration Site Conditions: frequent – asthenia; infrequent – peripheral edema, chest pain; rare – face edema

  • Hepatobiliary Disorders: rare – hepatitis, jaundice

  • Immune System Disorders: rare- hypersensitivity

  • Injury, Poisoning, and Procedural Complications: infrequent – fall; rare – heatstroke

  • Investigations: frequent – weight decreased; infrequent – hepatic enzyme increased, blood glucose increased, blood lactate dehydrogenase increased, gamma glutamyl transferase increased; rare – blood prolactin increased, blood urea increased, blood creatinine increased, blood bilirubin increased, electrocardiogram QT prolonged, glycosylated hemoglobin increased

  • Metabolism and Nutrition Disorders: frequent – anorexia; rare – hypokalemia, hyponatremia, hypoglycemia

  • Musculoskeletal and Connective Tissue Disorders: infrequent – muscular weakness, muscle tightness; rare – rhabdomyolysis, mobility decreased

  • Nervous System Disorders: infrequent – parkinsonism, memory impairment, cogwheel rigidity, hypokinesia, bradykinesia; rare – akinesia, myoclonus, coordination abnormal, speech disorder, grand mal convulsion; <1/10,000 patients - choreoathetosis

  • Psychiatric Disorders: infrequent – aggression, loss of libido, delirium; rare – libido increased, anorgasmia, tic, homicidal ideation, catatonia, sleep walking

  • Renal and Urinary Disorders: rare – urinary retention, nocturia

  • Reproductive System and Breast Disorders: infrequent – erectile dysfunction; rare – gynaecomastia, menstruation irregular, amenorrhea, breast pain, priapism

  • Respiratory, Thoracic, and Mediastinal Disorders: infrequent – nasal congestion, dyspnea

  • Skin and Subcutaneous Tissue Disorders: infrequent – rash, hyperhidrosis, pruritus, photosensitivity reaction, alopecia; rare – urticaria

  • Vascular Disorders: infrequent – hypotension, hypertension

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of aripiprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups, blood glucose fluctuation, oculogyric crisis and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Drug Interactions

Drugs Having Clinically Important Interactions with Abilify Mycite

Table 13 below includes clinically important drug interactions with Abilify Mycite.

Table 13: Clinically Important Drug Interactions with Abilify Mycite

Concomitant Drug Name or Drug ClassClinical RationaleClinical Recommendation
Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin) or strong CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine)The concomitant use of aripiprazole with strong CYP3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of aripiprazole alone [see Clinical Pharmacology (12.3)] .With concomitant use of Abilify Mycite with a strong CYP3A4 inhibitor or CYP2D6 inhibitor, reduce the Abilify Mycite dosage [see Dosage and Administration (2.6)] .
Strong CYP3A4 Inducers (e.g., carbamazepine, rifampin)The concomitant use of aripiprazole and carbamazepine decreased the exposure of aripiprazole compared to the use of aripiprazole alone [see Clinical Pharmacology (12.3)] .With concomitant use of Abilify Mycite with a strong CYP3A4 inducer, consider increasing the Abilify Mycite dosage [see Dosage and Administration (2.6)] .
Antihypertensive DrugsDue to its alpha adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.Monitor blood pressure and adjust dose accordingly [see Warnings and Precautions (5.8)] .
Benzodiazepines (e.g., lorazepam)The intensity of sedation was greater with the combination of oral aripiprazole and lorazepam as compared to that observed with aripiprazole alone. The orthostatic hypotension observed was greater with the combination as compared to that observed with lorazepam alone [see Warnings and Precautions (5.8)]Monitor sedation and blood pressure. Adjust dose accordingly.

Drugs Having No Clinically Important Interactions with Abilify Mycite

Based on pharmacokinetic studies, no dosage adjustment of Abilify Mycite is required when administered concomitantly with famotidine, valproate, lithium, lorazepam.

In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin, escitalopram), or CYP3A4 (e.g., dextromethorphan) when co-administered with Abilify Mycite. Additionally, no dosage adjustment is necessary for valproate, lithium, lamotrigine, lorazepam, or sertraline when co-administered with Abilify Mycite [see Clinical Pharmacology (12.3)] .

الاستخدام في مجموعات محددة

حمل

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Abilify Mycite during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.

ملخص المخاطر

Neonates exposed to antipsychotic drugs, including Abilify Mycite, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms [see Clinical Considerations]. There are no available data on aripiprazole use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies were conducted with aripiprazole in rats and rabbits during organogenesis, and in rats during the pre-and post-natal period. Oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses higher than the maximum recommended human dose (MRHD) produced fetal death, decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal abnormalities, and diaphragmatic hernia. Oral and intravenous aripiprazole administration during the pre- and post-natal period in rats at doses higher than the maximum recommended human dose (MRHD) produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival. Consider the benefits and risks of Abilify Mycite and possible risks to the fetus when prescribing Abilify Mycite to a pregnant woman. Advise pregnant women of potential fetal risk.

The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

اعتبارات سريرية

Fetal/Neonatal Adverse Reactions

Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs (including aripiprazole) during the third trimester of pregnancy. These symptoms have varied in severity. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms.

البيانات

Animal Data

In animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits.

Pregnant rats were treated with oral doses of 3, 10, and 30 mg/kg/day (1, 3, and 10 times the maximum recommended human dose [MRHD] on a mg/m 2 basis) of aripiprazole during the period of organogenesis. Gestation was slightly prolonged at 30 mg/kg/day. Treatment at the high dose of 30 mg/kg/day caused a slight delay in fetal development (decreased fetal weight), undescended testes, and delayed skeletal ossification (also seen at 10 mg/kg/day). There were no adverse effects on embryofetal or pup survival. Delivered offspring had decreased body weights (10 and 30 mg/kg/day) and increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia at 30 mg/kg (the other dose groups were not examined for these findings). Postnatally, delayed vaginal opening was seen at 10 and 30 mg/kg/day and impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) was seen at 30 mg/kg/day. Some maternal toxicity was seen at 30 mg/kg/day however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity.

In pregnant rats receiving aripiprazole injection intravenously (3, 9, and 27 mg/kg/day) during the period of organogenesis, decreased fetal weight and delayed skeletal ossification were seen at the highest dose where it also caused maternal toxicity.

Pregnant rabbits were treated with oral doses of 10, 30, and 100 mg/kg/day (2 , 3, and 11 times human exposure at MRHD based on AUC and 6, 19, and 65 times the MRHD based on mg/m 2) of aripiprazole during the period of organogenesis. At the high dose of 100 mg/kg/day decreased maternal food consumption, and increased abortions were seen as well as increased fetal mortality, decreased fetal weight (also seen at 30 mg/kg/day), increased incidence of a skeletal abnormality (fused sternebrae) (also seen at 30 mg/kg/day).

In pregnant rabbits receiving aripiprazole injection intravenously (3, 10, and 30 mg/kg/day) during the period of organogenesis, the highest dose, which caused pronounced maternal toxicity, resulted in decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased fetal skeletal ossification. The fetal no-effect dose was 10 mg/kg/day, which is 5 times the human exposure at the MRHD based on AUC and is 6 times the MRHD based on mg/m 2.

In a study in which rats were treated peri- and post-natally with oral doses of 3, 10, and 30 mg/kg/day (1, 3, and 10 times the MRHD on a mg/m 2 basis) of aripiprazole from gestation day 17 through day 21 postpartum, slight maternal toxicity, slightly prolonged gestation an increase in stillbirths and decreases in pup weight (persisting into adulthood) and survival were seen at 30 mg/kg/day.

In rats receiving aripiprazole injection intravenously (3, 8, and 20 mg/kg/day) from gestation day 6 through day 20 postpartum, an increase in stillbirths was seen at 8 and 20 mg/kg/day, and decreases in early postnatal pup weights and survival were seen at 20 mg/kg/day; these effects were seen in presence of maternal toxicity. There were no effects on postnatal behavioral and reproductive development.

The effect of Abilify Mycite on labor and delivery in humans is unknown.

الرضاعة

ملخص المخاطر

Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, the effects on the breastfed infant, or the effects on milk production.

The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Abilify Mycite and any potential adverse effects on the breastfed infant from Abilify Mycite or from the underlying maternal condition.

استخدام الأطفال

Safety and effectiveness of Abilify Mycite in pediatric patients have not been established.

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning,and Warnings and Precautions (5.2)].

استخدام الشيخوخة

No dosage adjustment of Abilify Mycite is recommended for elderly patients for the approved indications [see Boxed Warning, Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)] .

Of the 13,543 patients treated with oral aripiprazole in clinical trials, 1073 (8%) were ≥65 years old and 799 (6%) were ≥75 years old. Placebo-controlled studies of oral aripiprazole in schizophrenia, bipolar mania, or major depressive disorder did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Elderly patients treated with antipsychotic drugs with dementia-related psychosis had a greater incidence of stroke and transient ischemic attack. Abilify Mycite is not approved for the treatment of elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.1, 5.3)] .

CYP2D6 Poor Metabolizers

Abilify Mycite dosage adjustment is recommended in known CYP2D6 poor metabolizers due to high aripiprazole concentrations. Approximately 8% of Caucasians and 3 to 8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM) [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3)].

Hepatic and Renal Impairment

No dosage adjustment for Abilify Mycite is required on the basis of a patient’s hepatic function (mild to severe hepatic impairment, Child-Pugh score between 5 and 15) or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 mL/minute) [see Clinical Pharmacology (12.3)] .

Other Specific Populations

No dosage adjustment for Abilify Mycite is required on the basis of a patient’s sex, race, or smoking status [see Clinical Pharmacology (12.3)] .

Drug Abuse and Dependence

Controlled Substance

Abilify Mycite is not a controlled substance.

Abuse

Abilify Mycite has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of Abilify Mycite misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior).

Dependence

In physical dependence studies in monkeys, withdrawal symptoms were observed upon abrupt cessation of dosing. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed.

جرعة مفرطة

Human Experience

In clinical trials and in postmarketing experience, adverse reactions of deliberate or accidental overdosage with oral aripiprazole have been reported worldwide. These include overdoses with oral aripiprazole alone and in combination with other substances.

Common adverse reactions (reported in at least 5% of all overdose cases) reported with oral aripiprazole overdosage (alone or in combination with other substances) include vomiting, somnolence, and tremor. Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia.

Management of Overdosage

No specific information is available on the treatment of overdose with Abilify Mycite. If over-exposure occurs call your poison control center at 1-800-222-1222. An electrocardiogram should be obtained in case of overdosage and if QT interval prolongation is present, cardiac monitoring should be instituted. Otherwise, management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers.

Charcoal: In the event of an overdose of Abilify Mycite, an early charcoal administration may be useful in partially preventing the absorption of aripiprazole. Administration of 50 g of activated charcoal, one hour after a single 15 mg oral dose of aripiprazole, decreased the mean AUC and C max of aripiprazole by 50%.

Hemodialysis: Although there is no information on the effect of hemodialysis in treating an overdose with aripiprazole, hemodialysis is unlikely to be useful in overdose management since aripiprazole is highly bound to plasma proteins.

Abilify Mycite Description

Abilify Mycite is a drug-device combination product containing aripiprazole, an atypical antipsychotic, embedded with an Ingestible Event Marker (IEM) sensor.

Aripiprazole is 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyril. The empirical formula is C 23H 27Cl 2N 3O 2 and its molecular weight is 448.38. The chemical structure is:

Abilify Mycite is available in 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg strength tablets with sensor. Inactive ingredients of the tablets include cornstarch, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. Colorants include ferric oxide (yellow or red) and FD&C Blue No. 2 Aluminum Lake. Ingredients of the IEM include aluminum, cuprous chloride, ethyl cellulose, gold, hydroxypropyl cellulose, magnesium, silicon, silicon dioxide, silicon nitride, titanium-tungsten, titanium and triethyl citrate.

The Abilify Mycite System is a drug-device combination product composed of the following components:

  • An aripiprazole tablet with an embedded Ingestible Event Marker (IEM) sensor. The IEM is a 1 mm sized sensor embedded in the Abilify Mycite tablet. Upon contact with gastric fluid, magnesium and cuprous chloride within the IEM react to activate and power the device. The IEM then communicates to the MYCITE Patch, to track aripiprazole ingestion.
  • A MYCITE Patch (wearable sensor) is designed to detect the ingestion of the Abilify Mycite tablet, record the ingestion of the IEM, and transmit ingestion data to the mobile patient application (app).
  • A compatible mobile patient application (app) displays this data to allow patients to review their medication ingestion. These data can be shared with healthcare providers and caregivers.
  • Web-based portal or dashboard for healthcare professionals (HCP) and caregivers.

Abilify Mycite – Clinical Pharmacology

آلية العمل

The mechanism of action of aripiprazole in the treatment of schizophrenia, bipolar I disorder, or adjunctive treatment of major depressive disorder is unknown. However, the efficacy of aripiprazole could be mediated through a combination of partial agonist activity at D 2 and 5-HT 1A receptors and antagonist activity at 5-HT 2A receptors.

الديناميكا الدوائية

Aripiprazole exhibits high affinity for dopamine D 2 and D 3, serotonin 5-HT 1A and 5-HT 2A receptors (K i values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate affinity for dopamine D 4, serotonin 5-HT 2C and 5-HT 7, alpha1-adrenergic and histamine H 1 receptors (K i values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (K i=98 nM). Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC 50>1000 nM). Actions at receptors other than D 2, 5-HT 1A, and 5-HT 2A may explain some of the adverse reactions of aripiprazole (e.g., the orthostatic hypotension observed with aripiprazole may be explained by its antagonist activity at adrenergic alpha1 receptors).

الدوائية

Aripiprazole activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which has been shown to have affinities for D 2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma. The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both active moieties. Aripiprazole accumulation is predictable from single-dose pharmacokinetics. At steady-state, the pharmacokinetics of aripiprazole is dose-proportional. Elimination of aripiprazole is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP3A4. For CYP2D6 poor metabolizers, the mean elimination half-life for aripiprazole is about 146 hours.

استيعاب

Aripiprazole is well absorbed after administration of the tablet, with peak plasma concentrations occurring within 3 hours to 5 hours; the absolute oral bioavailability of the tablet formulation is 87%. Abilify Mycite can be administered with or without food. Administration of a 15 mg aripiprazole tablet with a standard high-fat meal did not significantly affect the C max or AUC of aripiprazole or its active metabolite, dehydro-aripiprazole, but delayed T max by 3 hours for aripiprazole and 12 hours for dehydro-aripiprazole.

توزيع

The steady-state volume of distribution of aripiprazole following intravenous administration is high (404 L or 4.9 L/kg), indicating extensive extravascular distribution. At therapeutic concentrations, aripiprazole and its major metabolite are greater than 99% bound to serum proteins, primarily to albumin. In healthy human volunteers administered 0.5 to 30 mg/day aripiprazole for 14 days, there was dose-dependent D 2 receptor occupancy indicating brain penetration of aripiprazole in humans.

إزالة

التمثيل الغذائي

Aripiprazole is metabolized primarily by three biotransformation pathways: dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4. Aripiprazole is the predominant drug moiety in the systemic circulation. At steady-state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma.

Excretion

Following a single oral dose of [14C]-labeled aripiprazole, approximately 25% and 55% of the administered radioactivity was recovered in the urine and feces, respectively. Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces.

Drug Interaction Studies

Effects of other drugs on the exposures of aripiprazole and dehydro-aripiprazole are summarized in Figure 1 and Figure 2, respectively. Based on simulation, a 4.5-fold increase in mean C max and AUC values at steady-state is expected when extensive metabolizers of CYP2D6 are administered with both strong CYP2D6 and CYP3A4 inhibitors. A 3-fold increase in mean C max and AUC values at steady-state is expected in poor metabolizers of CYP2D6 administered with strong CYP3A4 inhibitors.

Figure 1: The Effects of Other Drugs on Aripiprazole Pharmacokinetics

Figure 2: The Effects of Other Drugs on Dehydro-aripiprazole Pharmacokinetics

The effects of aripiprazole on the exposures of other drugs are summarized in Figure 3. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 or 40 mg/day), paroxetine CR (37.5 or 50 mg/day), or sertraline (100 or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.

Figure 3: The Effects of Aripiprazole on Pharmacokinetics of Other Drugs

السكان محددة

Exposures of aripiprazole and dehydro-aripiprazole in specific populations are summarized in Figure 4 and Figure 5, respectively.

Figure 4: Effects of Intrinsic Factors on Aripiprazole Pharmacokinetics

Figure 5: Effects of Intrinsic Factors on Dehydro-aripiprazole Pharmacokinetics

علم السموم غير السريري

التسرطن ، الطفرات ، ضعف الخصوبة

Carcinogenesis

Lifetime carcinogenicity studies were conducted in ICR mice, Sprague-Dawley (SD) rats, and F344 rats. Aripiprazole was administered for 2 years in the diet at doses of 1, 3, 10, and 30 mg/kg/day to ICR mice and 1, 3, and 10 mg/kg/day to F344 rats (0.2 to 5 times and 0.3 to 3 times the maximum recommended human dose [MRHD] based on mg/m 2, respectively). In addition, SD rats were dosed orally for 2 years at 10, 20, 40, and 60 mg/kg/day (3 to 19 times the MRHD based on mg/m 2). Aripiprazole did not induce tumors in male mice or male rats. In female mice, the incidences of pituitary gland adenomas and mammary gland adenocarcinomas and adenoacanthomas were increased at dietary doses of 3 to 30 mg/kg/day (0.1 to 0.9 times human exposure at MRHD based on AUC and 0.5 to 5 times the MRHD based on mg/m 2). In female rats, the incidence of mammary gland fibroadenomas was increased at a dietary dose of 10 mg/kg/day (0.1 times human exposure at MRHD based on AUC and 3 times the MRHD based on mg/m 2); and the incidences of adrenocortical carcinomas and combined adrenocortical adenomas/carcinomas were increased at an oral dose of 60 mg/kg/day (14 times human exposure at MRHD based on AUC and 19 times the MRHD based on mg/m 2).

Proliferative changes in the pituitary and mammary gland of rodents have been observed following chronic administration of other antipsychotic agents and are considered prolactin-mediated. Serum prolactin was not measured in the aripiprazole carcinogenicity studies. However, increases in serum prolactin levels were observed in female mice in a 13-week dietary study at the doses associated with mammary gland and pituitary tumors. Serum prolactin was not increased in female rats in 4-week and 13-week dietary studies at the dose associated with mammary gland tumors. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unknown.

Mutagenesis

The mutagenic potential of aripiprazole was tested in the in vitro bacterial reverse-mutation assay, the in vitro bacterial DNA repair assay, the in vitro forward gene mutation assay in mouse lymphoma cells, the in vitro chromosomal aberration assay in Chinese hamster lung (CHL) cells, the in vivo micronucleus assay in mice, and the unscheduled DNA synthesis assay in rats. Aripiprazole and a metabolite (2,3-DCPP) were clastogenic in the in vitro chromosomal aberration assay in CHL cells with and without metabolic activation. The metabolite, 2,3-DCPP, produced increases in numerical aberrations in the in vitro assay in CHL cells in the absence of metabolic activation. A positive response was obtained in the in vivo micronucleus assay in mice; however, the response was due to a mechanism not considered relevant to humans.

Impairment of Fertility

Female rats were treated with oral doses of 2, 6, and 20 mg/kg/day (0.6, 2, and 6 times the MRHD on a mg/m 2 basis) of aripiprazole from 2 weeks prior to mating through day 7 of gestation. Estrus cycle irregularities and increased corpora lutea were seen at all doses, but no impairment of fertility was seen. Increased pre-implantation loss was seen at 6 and 20 mg/kg/day and decreased fetal weight was seen at 20 mg/kg/day.

Male rats were treated with oral doses of 20, 40, and 60 mg/kg/day (6, 13, and 19 times the MRHD on a mg/m 2 basis) of aripiprazole from 9 weeks prior to mating through mating. Disturbances in spermatogenesis were seen at 60 mg/kg and prostate atrophy was seen at 40 and 60 mg/kg, but no impairment of fertility was seen.

علم السموم و / أو علم الأدوية

Aripiprazole produced retinal degeneration in albino rats in a 26-week chronic toxicity study at a dose of 60 mg/kg and in a 2-year carcinogenicity study at doses of 40 and 60 mg/kg. The 40 and 60 mg/kg/day doses are 13 and 19 times the maximum recommended human dose (MRHD) based on mg/m 2 and 7 to 14 times human exposure at MRHD based on AUC. Evaluation of the retinas of albino mice and of monkeys did not reveal evidence of retinal degeneration. Additional studies to further evaluate the mechanism have not been performed. The relevance of this finding to human risk is unknown.

الدراسات السريرية

The safety and efficacy of aripiprazole tablets for the treatment of adults with schizophrenia, acute treatment of adults with manic and mixed episodes associated with Bipolar I disorder, and adjunctive treatment of adults with major depressive disorder (MDD) has been established and is based on the following adequate and well-controlled trials of aripiprazole tablets:

  • Four short-term trials and one maintenance trial in adult patients with schizophrenia [see Clinical Studies (14.1)]
  • Four short-term monotherapy trials and one 6-week adjunctive trial in adult patients with manic or mixed episodes [see Clinical Studies (14.2)]
  • One maintenance monotherapy trial and in one maintenance adjunctive trial in adult patients with bipolar I disorder [see Clinical Studies (14.2)]
  • Two short-term trials in adult patients with MDD who had an inadequate response to antidepressant therapy during the current episode [see Clinical Studies (14.3)]

Schizophrenia

The efficacy of aripiprazole tablets in the treatment of schizophrenia was evaluated in five short-term (4-week and 6-week), placebo-controlled trials of acutely relapsed inpatients who predominantly met DSM-III/IV criteria for schizophrenia. Four of the five trials were able to distinguish aripiprazole tablets from placebo, but one study, the smallest, did not. Three of these studies also included an active control group consisting of either risperidone (one trial) or haloperidol (two trials), but they were not designed to allow for a comparison of aripiprazole tablets and the active comparators.

In the four positive trials for aripiprazole tablets, four primary measures were used for assessing psychiatric signs and symptoms. Efficacy was evaluated using the total score on the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30-item scale that measures positive symptoms of schizophrenia (7 items), negative symptoms of schizophrenia (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); total PANSS scores range from 30 to 210. The Clinical Global Impression (CGI) assessment reflects the impression of a skilled observer, fully familiar with the manifestations of schizophrenia, about the overall clinical state of the patient.

In a 4-week trial (n=414) comparing two fixed doses of aripiprazole tablets (15 or 30 mg/day) to placebo, both doses of aripiprazole tablets were superior to placebo in the PANSS total score (Study 1 in Table 14), PANSS positive subscale, and CGI-severity score. In addition, the 15 mg dose was superior to placebo in the PANSS negative subscale.

In a 4-week trial (n=404) comparing two fixed doses of aripiprazole tablets (20 or 30 mg/day) to placebo, both doses of aripiprazole tablets were superior to placebo in the PANSS total score (Study 2 in Table 14), PANSS positive subscale, PANSS negative subscale, and CGI-severity score.

In a 6-week trial (n=420) comparing three fixed doses of aripiprazole tablets (10, 15, or 20 mg/day) to placebo, all three doses of aripiprazole tablets were superior to placebo in the PANSS total score (Study 3 in Table 14), PANSS positive subscale, and the PANSS negative subscale.

In a 6-week trial (n=367) comparing three fixed doses of aripiprazole tablets (2, 5, or 10 mg/day) to placebo, the 10 mg dose of aripiprazole tablets was superior to placebo in the PANSS total score (Study 4 in Table 14), the primary outcome measure of the study. The 2 and 5 mg doses did not demonstrate superiority to placebo on the primary outcome measure.

Thus, the efficacy of 10, 15, 20, and 30 mg daily doses was established in two studies for each dose. Among these doses, there was no evidence that the higher dose groups offered any advantage over the lowest dose group of these studies.

An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age, gender, or race.

A longer-term trial enrolled 310 inpatients or outpatients meeting DSM-IV criteria for schizophrenia who were, by history, symptomatically stable on other antipsychotic medications for periods of 3 months or longer. These patients were discontinued from their antipsychotic medications and randomized to aripiprazole tablets 15 mg/day or placebo for up to 26 weeks of observation for relapse. Relapse during the double-blind phase was defined as CGI-Improvement score of ≥5 (minimally worse), scores ≥5 (moderately severe) on the hostility or uncooperativeness items of the PANSS, or ≥20% increase in the PANSS total score. Patients receiving aripiprazole tablets 15 mg/day experienced a significantly longer time to relapse over the subsequent 26 weeks compared to those receiving placebo (Study 5 in Figure 6).

Table 14: Schizophrenia Studies

Study NumberTreatment GroupPrimary Efficacy Measure: PANSS
Mean Baseline Score (SD)LS Mean Change from Baseline (SE)Placebo-subtracted Difference * (95% CI)
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.

*
Difference (drug minus placebo) in least-squares mean change from baseline

Doses statistically significantly superior to placebo

Study 1Aripiprazole tablets (15 mg/day) †98.5 (17.2)-15.5 (2.40)-12.6 (-18.9, -6.2)
Aripiprazole tablets (30 mg/day) †99.0 (19.2)-11.4 (2.39)-8.5 (-14.8, -2.1)
Placebo100.2 (16.5)-2.9 (2.36)
Study 2Aripiprazole tablets (20 mg/day) †92.6 (19.5)-14.5 (2.23)-9.6 (-15.4, -3.8)
Aripiprazole tablets (30 mg/day) †94.2 (18.5)-13.9 (2.24)-9.0 (-14.8, -3.1)
Placebo94.3 (18.5)-5.0 (2.17)
Study 3Aripiprazole tablets (10 mg/day) †92.7 (19.5)-15.0 (2.38)-12.7 (-19.00, -6.41)
Aripiprazole tablets (15 mg/day) †93.2 (21.6)-11.7 (2.38)-9.4 (-15.71, -3.08)
Aripiprazole tablets (20 mg/day) †92.5 (20.9)-14.4 (2.45)-12.1 (-18.53, -5.68)
Placebo92.3 (21.8)-2.3 (2.35)
Study 4Aripiprazole tablets (2 mg/day)90.7 (14.5)-8.2 (1.90)-2.9 (-8.29, 2.47)
Aripiprazole tablets (5 mg/day)92.0 (12.6)-10.6 (1.93)-5.2 (-10.7, 0.19)
Aripiprazole tablets (10 mg/day) †90.0 (11.9)-11.3 (1.88)-5.9 (-11.3, -0.58)
Placebo90.8 (13.3)-5.3 (1.97)

Figure 6: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse (Schizophrenia Study 5)

Bipolar Disorder

Acute Treatment of Manic and Mixed Episodes

Monotherapy

The efficacy of aripiprazole tablets as monotherapy in the acute treatment of manic and mixed episodes associated with bipolar I disorder was established in four 3-week placebo-controlled trials in hospitalized patients who met the DSM-IV criteria for bipolar I disorder with manic or mixed episodes. These studies included patients with or without psychotic features and two of the studies also included patients with or without a rapid-cycling course.

The primary instrument used for assessing manic symptoms was the Young Mania Rating Scale (Y-MRS), an 11-item clinician-rated scale traditionally used to assess the degree of manic symptomatology in a range from 0 (no manic features) to 60 (maximum score). A key secondary instrument included the Clinical Global Impression-Bipolar (CGI-BP) Scale.

In the four positive, 3-week placebo-controlled trials (n=268; n=248; n=480; n=485) which evaluated aripiprazole tablets in a range of 15 mg to 30 mg, once daily (with a starting dose of 30 mg/day in two studies and 15 mg/day in two studies), aripiprazole tablets were superior to placebo in the reduction of Y-MRS total score (Studies 1 to 4 in Table 15) and CGI-BP Severity of Illness score (mania). In the two studies with a starting dose of 15 mg/day, 48% and 44% of patients were on 15 mg/day at endpoint. In the two studies with a starting dose of 30 mg/day, 86% and 85% of patients were on 30 mg/day at endpoint.

Adjunctive Therapy

The efficacy of adjunctive aripiprazole tablets with concomitant lithium or valproate in the treatment of manic or mixed episodes associated with Bipolar I Disorder was established in a 6-week placebo-controlled study (n=384) with a 2-week lead-in mood stabilizer monotherapy phase in adult patients who met DSM-IV criteria for bipolar I disorder. This study included patients with manic or mixed episodes and with or without psychotic features.

Patients were initiated on open-label lithium (0.6 to 1.0 mEq/L) or valproate (50 to 125 μg/mL) at therapeutic serum levels and remained on stable doses for 2 weeks. At the end of 2 weeks, patients demonstrating inadequate response (Y-MRS total score ≥16 and ≤25% improvement on the Y-MRS total score) to lithium or valproate were randomized to receive either aripiprazole tablets (15 mg/day or an increase to 30 mg/day as early as day 7) or placebo as adjunctive therapy with open-label lithium or valproate. In the 6-week placebo-controlled phase, adjunctive aripiprazole tablets starting at 15 mg/day with concomitant lithium or valproate (in a therapeutic range of 0.6 to 1.0 mEq/L or 50 to 125 μg/mL, respectively) was superior to lithium or valproate with adjunctive placebo in the reduction of the Y-MRS total score (Study 5 in Table 15) and CGI-BP Severity of Illness score (mania). Seventy-one percent of the patients coadministered valproate and 62% of the patients coadministered lithium were on 15 mg/day at 6-week endpoint.

Table 15: Bipolar Studies

Study NumberTreatment GroupPrimary Efficacy Measure: Y-MRS
Mean Baseline Score (SD)LS Mean Change from Baseline (SE)Placebo-subtracted Difference * (95% CI)
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.

*
Difference (drug minus placebo) in least-squares mean change from baseline.

Doses statistically significantly superior to placebo.

Study 1Aripiprazole tablets (30/15 mg/day) †29.0 (5.9)-12.52 (1.05)-5.33 (-7.90, -2.76)
Placebo28.5 (4.6)-7.19 (1.07)
Study 2Aripiprazole tablets (30/15  mg/day) †27.8 (5.7)-8.15 (1.23)-4.80 (-7.80, -1.80)
Placebo29.1 (6.9)-3.35(1.22)
Study 3Aripiprazole tablets (15 to 30 mg/day) †28.5 (5.6)-12.64 (0.84)-3.63 (-5.75 , -1.51)
Placebo28.9 (5.9)9.01 (0.81)
Study 4Aripiprazole tablets (15 to 30 mg/day) †28.0 (5.8)-11.98 (0.80)-2.28 (-4.44 , -0.11)
Placebo28.3 (5.8)-9.70 (0.83)
Study 5Aripiprazole tablets (15 or 30 mg/day) † + Lithium/Valproate23.2 (5.7)-13.31 (0.50)-2.62 (-4.29 , -0.95)
Placebo + Lithium/Valproate23.0 (4.9)-10.70 (0.69)

Maintenance Treatment of Bipolar I Disorder

Monotherapy Maintenance Therapy

A maintenance trial was conducted in adult patients meeting DSM-IV criteria for bipolar I disorder with a recent manic or mixed episode who had been stabilized on open-label aripiprazole tablets and who had maintained a clinical response for at least 6 weeks. The first phase of this trial was an open-label stabilization period in which inpatients and outpatients were clinically stabilized and then maintained on open-label aripiprazole tablets (15 or 30 mg/day, with a starting dose of 30 mg/day) for at least 6 consecutive weeks. One hundred sixty-one outpatients were then randomized in a double-blind fashion to either the same dose of aripiprazole tablets they were on at the end of the stabilization and maintenance period or placebo and were then monitored for manic or depressive relapse. During the randomization phase, aripiprazole tablets were superior to placebo on time to the number of combined affective relapses (manic plus depressive), the primary outcome measure for this study (Study 7 in Figure 7). A total of 55 mood events were observed during the double-blind treatment phase. Nineteen were from the aripiprazole tablets group and 36 were from the placebo group. The number of observed manic episodes in the aripiprazole tablets group (6) were fewer than that in the placebo group (19), while the number of depressive episodes in the aripiprazole tablets group (9) was similar to that in the placebo group (11).

An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender; however, there were insufficient numbers of patients in each of the ethnic groups to adequately assess inter-group differences.

Figure 7: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse (Bipolar Study 7)

Adjunctive Maintenance Therapy

An adjunctive maintenance trial was conducted in adult patients meeting DSM-IV criteria for bipolar I disorder with a recent manic or mixed episode. Patients were initiated on open-label lithium (0.6 to 1.0 mEq/L) or valproate (50 to 125 μg/mL) at therapeutic serum levels, and remained on stable doses for 2 weeks. At the end of 2 weeks, patients demonstrating inadequate response (Y-MRS total score ≥16 and ≤35% improvement on the Y-MRS total score) to lithium or valproate received aripiprazole tablets with a starting dose of 15 mg/day with the option to increase to 30 mg or reduce to 10 mg as early as day 4, as adjunctive therapy with open-label lithium or valproate. Prior to randomization, patients on the combination of single-blind aripiprazole tablets and lithium or valproate were required to maintain stability (Y-MRS and MADRS total scores ≤12) for 12 consecutive weeks. Three hundred thirty-seven patients were then randomized in a double-blind fashion, to either the same dose of aripiprazole tablets they were on at the end of the stabilization period or placebo plus lithium or valproate and were then monitored for manic, mixed, or depressive relapse for a maximum of 52 weeks. Aripiprazole tablets were superior to placebo on the primary endpoint, time from randomization to relapse to any mood event (Study 8 in Figure 8). A mood event was defined as hospitalization for a manic, mixed, or depressive episode, study discontinuation due to lack of efficacy accompanied by Y-MRS score >16 and/or a MADRS >16, or an SAE of worsening disease accompanied by Y-MRS score >16 and/or a MADRS >16. A total of 68 mood events were observed during the double-blind treatment phase. Twenty-five were from the aripiprazole group and 43 were from the placebo group. The number of observed manic episodes in the aripiprazole group (7) were fewer than that in the placebo group (19), while the number of depressive episodes in the aripiprazole group (14) was similar to that in the placebo group (18). The Kaplan-Meier curves of the time from randomization to relapse to any mood event during the 52-week double-blind treatment phase for aripiprazole tablets and placebo groups are shown in Figure 8.

An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender; however, there were insufficient numbers of patients in each of the ethnic groups to adequately assess inter-group differences.

Figure 8: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse to Any Mood Event (Bipolar Study 8)

Adjunctive Treatment of Adults with Major Depressive Disorder

The efficacy of aripiprazole tablets in the adjunctive treatment of major depressive disorder (MDD) was demonstrated in two short-term (6-week), placebo-controlled trials of adult patients meeting DSM-IV criteria for MDD who had had an inadequate response to prior antidepressant therapy (1 to 3 courses) in the current episode and who had also demonstrated an inadequate response to 8 weeks of prospective antidepressant therapy (paroxetine extended-release, venlafaxine extended-release, fluoxetine, escitalopram, or sertraline). Inadequate response for prospective treatment was defined as less than 50% improvement on the 17-item version of the Hamilton Depression Rating Scale (HAMD17), minimal HAMD17 score of 14, and a Clinical Global Impressions Improvement rating of no better than minimal improvement. Inadequate response to prior treatment was defined as less than 50% improvement as perceived by the patient after a minimum of 6 weeks of antidepressant therapy at or above the minimal effective dose.

The primary instrument used for assessing depressive symptoms was the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale used to assess the degree of depressive symptomatology. The key secondary instrument was the Sheehan Disability Scale (SDS), a 3-item self-rated instrument used to assess the impact of depression on three domains of functioning with each item scored from 0 (not at all) to 10 (extreme).

In the two trials (n=381, n=362), aripiprazole tablets were superior to placebo in reducing mean MADRS total scores (Studies 1, 2 in Table 16). In one study, aripiprazole tablets were also superior to placebo in reducing the mean SDS score.

In both trials, patients received aripiprazole tablets adjunctive to antidepressants at a dose of 5 mg/day. Based on tolerability and efficacy, doses could be adjusted by 5 mg increments, one week apart. Allowable doses were: 2, 5, 10, 15 mg/day, and for patients who were not on potent CYP2D6 inhibitors fluoxetine and paroxetine, 20 mg/day. The mean final dose at the end point for the two trials was 10.7 and 11.4 mg/day.

An examination of population subgroups did not reveal evidence of differential response based on age, choice of prospective antidepressant, or race. With regards to gender, a smaller mean reduction on the MADRS total score was seen in males than in females.

Table 16: Adjunctive Treatment of Major Depressive Disorder Studies

Study NumberTreatment GroupPrimary Efficacy Measure: MADRS
Mean Baseline Score (SD)LS Mean Change from Baseline (SE)Placebo-subtracted Difference * (95% CI)
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.

*
Difference (drug minus placebo) in least-squares mean change from baseline.

Doses statistically significantly superior to placebo.

Study 1Aripiprazole tablets (5 to 20 mg/day) † + Antidepressant25.2(6.2)-8.49 (0.66)-2.84 (-4.53 , -1.15)
Placebo + Antidepressant27.0 (5.5)-5.65 (0.64)
Study 2Aripiprazole tablets (5 to 20 mg/day) † + Antidepressant26.0 (6.0)-8.78 (0.63)-3.01 (-4.66 , -1.37)
Placebo + Antidepressant26.0 (6.5)-5.77 (0.67)

كيفية التزويد / التخزين والتداول

How Supplied

The Abilify Mycite kit contains aripiprazole tablets embedded with an Ingestible Event Marker (IEM) sensor co-packaged with 7 MYCITE Patches (wearable sensors) in the presentations listed in Table 17.

Table 17: Abilify Mycite Kit Presentations

Tablet StrengthTablet Color/ShapeTablet MarkingsPack SizeNDC Code
2 mgpale green
modified rectangle
“DA-029” and “2”Bottle of 30 tablets +7 MYCITE Patches59148-029-85
5 mgpale blue
modified rectangle
“DA-030” and “5”Bottle of 30 tablets +7 MYCITE Patches59148-030-85
10 mgoff-white to pale pink
modified rectangle
“DA-031” and “10”Bottle of 30 tablets +7 MYCITE Patches59148-031-85
15 mgpale yellow
round
“DA-032” and “15”Bottle of 30 tablets +7 MYCITE Patches59148-032-85
20 mgwhite to pale yellowish white
round
“DA-033” and “20”Bottle of 30 tablets +7 MYCITE Patches59148-033-85
30 mgoff-white to pale pink
round
“DA-034” and “30”Bottle of 30 tablets +7 MYCITE Patches59148-034-85

تخزين

Tablet bottle:

Store 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Do not store in conditions where tablets are exposed to humid conditions.

MYCITE Patch (Wearable Sensor):

Store between 15°C and 30°C (59°F to 86°F), 15% to 93% relative humidity.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ).

General Instructions for Use

Instruct patients to refer to the app store to ensure compatibility with their specific smartphone. Instruct patient to first download the MYCITE APP and follow instructions provided by the app. Advise patients that the initial use should be facilitated by the healthcare provider.

Advise patients that most ingestions will be detected within 30 minutes; however, in some cases it can take over two hours for the smartphone app and web portal to detect the ingestion of Abilify Mycite. In some cases, the ingestion of the tablet may not be detected. If the tablet is not detected after ingestion, the dose should not be repeated.

Managing Lost or Disabled Mobile Device

Advise patients that if their smartphone is lost, impaired or otherwise rendered unusable, some information collected by the system (synced) may be lost. Advise patients to change their MYCITE Patch immediately and connect to a new mobile device using their current account information. Information previously synced to the patients account will be available.

Using the MYCITE Patch in Different Environments

The MYCITE Patch will communicate with a paired device when it is within 9-foot proximity. The MYCITE Patch should remain on an individual whether they are showering, swimming, or exercising as it is intended to tolerate water or perspiration. Patients undergoing an MRI, however, need to remove their patch and replace with a new one as soon as possible. In order for the MYCITE Patch to communicate with a smartphone, the device must be powered on and Bluetooth ®-enabled.

Suicidal Thoughts and Behaviors

Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down and instruct them to report such symptoms to the healthcare provider [see Boxed Warning, Warnings and Precautions (5.2)].

Neuroleptic Malignant Syndrome (NMS)

Counsel patients about a potentially fatal adverse reaction referred to as Neuroleptic Malignant Syndrome (NMS) that has been reported in association with administration of antipsychotic drugs. Advise patients to contact a healthcare provider or report to the emergency room if they experience signs or symptoms of NMS [see Warnings and Precautions (5.4)].

Tardive Dyskinesia

Advise patients that abnormal involuntary movements have been associated with the administration of antipsychotic drugs. Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their healthcare provider if these abnormal movements occur [see Warnings and Precautions (5.5)].

Metabolic Changes

Educate patients about the risk of metabolic changes, how to recognize symptoms of hyperglycemia and diabetes mellitus, and the need for specific monitoring, including blood glucose, lipids, and weight [see Warnings and Precautions (5.6)].

Pathological Gambling and Other Compulsive Behaviors

Advise patients and their caregivers of the possibility that they may experience compulsive urges to shop, increased urges to gamble, compulsive sexual urges, binge eating and/or other compulsive urges and the inability to control these urges while taking aripiprazole. In some cases, but not all, the urges were reported to have stopped when the dose was reduced or stopped [see Warnings and Precautions (5.7)] .

Orthostatic Hypotension and Syncope

Educate patients about the risk of orthostatic hypotension and syncope especially early in treatment, when re-initiating treatment, or when increasing the dosage [see Warnings and Precautions (5.8)].

Leukopenia, Neutropenia and Agranulocytosis

Advise patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia that they should have their CBC monitored while taking Abilify Mycite [see Warnings and Precautions (5.10)].

Interference with Cognitive and Motor Performance

Because Abilify Mycite may have the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Abilify Mycite therapy does not affect them adversely [see Warnings and Precautions (5.12)] .

Heat Exposure and Dehydration

Counsel patients regarding appropriate care in avoiding overheating and dehydration [see Warnings and Precautions (5.13)] .

Concomitant Medication

Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions [see Drug Interactions (7)] .

حمل

Advise patients that Abilify Mycite may cause extrapyramidal and/or withdrawal symptoms in a neonate and to notify their healthcare provider with a known or suspected pregnancy. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Abilify Mycite during pregnancy [see Use In Specific Populations (8.1)].

Tablets manufactured by Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan

IEM sensors and MYCITE Patches Manufactured by Proteus Digital Health ®, Inc., 2600 Bridge Parkway, Redwood City, CA 94065 USA

Distributed and marketed by Otsuka America Pharmaceutical, Inc., Rockville, MD 20850 USA

Abilify Mycite ® and MYCITE ® are registered trademarks of Otsuka Pharmaceutical Co., Ltd.

©2020, Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan

This Medication Guide has been approved by the U.S. Food and Drug Administration.Issued: 02/2020
MEDICATION GUIDE
Abilify Mycite ® (a BIL ĭ fī – Mi SIHYT)
(aripiprazole tablets with sensor)
  • Important:
  • If you are taking Abilify Mycite with other medicines for treatment of major depressive disorder (MDD), you should also read the Medication Guides or Patient Information that comes with the other medicines.
  • The Abilify Mycite System has 4 parts:

    • Aripiprazole tablet with an Ingestible Event Marker (IEM) sensor inside it (Abilify Mycite).
    • MYCITE Patch (wearable sensor) that picks up (detects) the signal from the IEM sensor after you take the Abilify Mycite tablet and sends the information to a smartphone.
    • MYCITE APP, which is a smartphone application (app) that is used with a compatible smartphone to show information about when you take your Abilify Mycite tablet.
    • Web-based portal for healthcare providers and caregivers.
  • Download the MYCITE APP before using the Abilify Mycite System. Always follow the instructions provided within the MYCITE APP when using the Abilify Mycite System.
  • Your healthcare provider should show you how to use the Abilify Mycite System before you use it for the first time.

What is the most important information I should know about Abilify Mycite?
Abilify Mycite may cause serious side effects, including:

  • Increased risk of death in elderly people with dementia-related psychosis. Medicines like Abilify Mycite can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Abilify Mycite is not approved for the treatment of people who have lost touch with reality (psychosis) due to confusion or memory loss (dementia).

  • Increased risk of suicidal thoughts or actions in children and young adults. Antidepressant medicines may increase suicidal thoughts or actions in some children and young adults within the first few months of treatment and when the dose is changed. It is not known if Abilify Mycite is safe and effective for use in children.

    • How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

      • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
      • Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
      • Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

What is Abilify Mycite?
Abilify Mycite is a prescription medicine of aripiprazole tablets with an Ingestible Event Marker (IEM) sensor inside it used:

  • To treat adults with schizophrenia
  • To treat bipolar I disorder:
    • short-term (acute) treatment of adults with manic or mixed episodes alone or when used with the medicine lithium or valproate
    • maintenance treatment of adults alone or when used with the medicine lithium or valproate
  • To treat adults with major depressive disorder (MDD) along with other antidepressant medicines

The Abilify Mycite System is meant to track if you have taken your Abilify Mycite.
It is not known if Abilify Mycite can improve how well you take your aripiprazole (patient compliance) or for changing your dose of aripiprazole.
There may be a delay in the detection of the Abilify Mycite tablet and sometimes the detection of the tablet might not happen at all. Abilify Mycite is not for use as real-time or emergency monitoring.
It is not known if Abilify Mycite is safe or effective for use in children.

Do not take Abilify Mycite if you are allergic to aripiprazole or any of the ingredients in Abilify Mycite. See the end of this Medication Guide for a complete list of ingredients in Abilify Mycite.

Before taking Abilify Mycite, tell your healthcare provider about all your medical conditions, including if you:

  • have diabetes or high blood sugar or have a family history of diabetes or high blood sugar. Your healthcare provider should check your blood sugar before you start and during treatment with Abilify Mycite.
  • have or had seizures (convulsions)
  • have or had low or high blood pressure
  • have or had heart problems or stroke
  • have or had a low white blood cell count
  • are pregnant or plan to become pregnant. Talk to your healthcare provider about the risk to your unborn baby if you take ABLIFY MYCITE during pregnancy.
    • Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with Abilify Mycite.
    • If you become pregnant during treatment with Abilify Mycite, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or go to http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
  • are breastfeeding or plan to breastfeed. Abilify Mycite can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with Abilify Mycite.

Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Abilify Mycite and other medicines may affect each other causing possible serious side effects. Abilify Mycite may affect the way other medicines work, and other medicines may affect how Abilify Mycite works.
Your healthcare provider can tell you if it is safe to take Abilify Mycite with your other medicines. Do not start or stop any other medicines during treatment with Abilify Mycite without talking to your healthcare provider first.
Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Abilify Mycite?

  • See the MYCITE APP for instructions about how to apply and wear the MYCITE Patch and how to use the Abilify Mycite System the right way.
  • Take Abilify Mycite exactly as your healthcare provider tells you to take it. Do not change the dose or stop taking Abilify Mycite without first talking to your healthcare provider.
  • Take Abilify Mycite by mouth with or without food.
  • Swallow Abilify Mycite tablets whole. Do not divide, crush, or chew Abilify Mycite tablets.
  • The Abilify Mycite tablet is usually detected within 30 minutes after you take it, but there may be a delay of more than 2 hours for the smartphone app and web portal to detect that you have taken Abilify Mycite, and sometimes the Abilify Mycite tablet might not be detected at all. If the tablet is not detected after you take it, do not repeat the dose.
  • If over-exposure occurs, call your poison control center at 1-800-222-1222.

What should I avoid while taking Abilify Mycite?

  • Do not drive, operate heavy machinery, or do other dangerous activities until you know how Abilify Mycite affects you. Abilify Mycite may make you drowsy.
  • Do not become too hot or dehydrated during treatment with Abilify Mycite.
    • Do not exercise too much.
    • In hot weather, stay inside in a cool place if possible.
    • Stay out of the sun.
    • Do not wear too much clothing or heavy clothing.
    • Drink plenty of water.

What are the possible side effects of Abilify Mycite?
Abilify Mycite may cause serious side effects, including:

  • See ” What is the most important information I should know about Abilify Mycite?”
  • Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death.

Neuroleptic malignant syndrome (NMS), a serious condition that can lead to death. Call your healthcare provider or go to the nearest hospital emergency room right away if you have some or all of the following signs and symptoms of NMS:

    • high fever
    • stiff muscles
    • الالتباس
    • sweating
    • changes in pulse, heart rate, and blood pressure
  • Uncontrolled body movements (tardive dyskinesia). Abilify Mycite may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking Abilify Mycite. Tardive dyskinesia may also start after you stop taking Abilify Mycite.

  • Problems with your metabolism such as:

    • high blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take Abilify Mycite. Extremely high blood sugar can lead to coma or death. If you have diabetes or risk factors for diabetes (such as being overweight or a family history of diabetes), your healthcare provider should check your blood sugar before you start and during your treatment with Abilify Mycite.
      Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with Abilify Mycite:

      • feel very thirsty
      • need to urinate more than usual
      • feel very hungry
      • feel weak or tired
      • feel sick to your stomach
      • feel confused, or your breath smells fruity
      • increased fat levels (cholesterol and triglycerides) in your blood.
      • weight gain. You and your healthcare provider should check your weight regularly.

  • Unusual urges. Some people taking Abilify Mycite have had unusual urges, such as gambling, binge eating or eating that you cannot control (compulsive), compulsive shopping and sexual urges. If you or your family members notice that you are having unusual urges or behaviors, talk to your healthcare provider.

  • Decreased blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.

  • Falls
  • Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with Abilify Mycite.

  • Seizures (convulsions)
  • Problems controlling your body temperature so that you feel too warm. See ” What should I avoid while taking Abilify Mycite?”

  • Difficulty swallowing

The most common side effects of Abilify Mycite in adults include:

  • restlessness or need to move (akathisia)
  • dizziness
  • nausea
  • insomnia
  • shaking (tremor)
  • anxiety
  • constipation
  • sedation

These are not all the possible side effects of Abilify Mycite.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Abilify Mycite?

  • Store Abilify Mycite tablets and MYCITE Patches at room temperature, between 68°F to 77°F (20°C to 25°C).
  • Keep Abilify Mycite tablets and MYCITE Patches (wearable sensor) dry. Do not store Abilify Mycite tablets and Patches (wearable sensor) in places with high humidity.

Keep Abilify Mycite and all medicines out of the reach of children.

General information about the safe and effective use of Abilify Mycite.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Abilify Mycite for a condition for which it was not prescribed. Do not give Abilify Mycite to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about Abilify Mycite that was written for healthcare professionals.

What are the ingredients in Abilify Mycite?
Active ingredient: aripiprazole
Inactive ingredients: cornstarch, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose, and Ingestible Event Marker (IEM). Colorants include ferric oxide (yellow or red) and FD&C Blue No. 2 Aluminum Lake. Ingredients of the IEM include aluminum, cuprous chloride, ethyl cellulose, gold, hydroxypropyl cellulose, magnesium, silicon, silicon dioxide, silicon nitride, titanium-tungsten, titanium and triethyl citrate.
صنع بواسطة:
Tablets manufactured by Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan
IEM and Patches Manufactured by Proteus Digital Health, Inc., 2600 Bridge Parkway, Redwood City, CA 94065 USA
Distributed and marketed by Otsuka America Pharmaceutical, Inc., Rockville, MD 20850 USA
Abilify Mycite ® and MYCITE ® are registered trademarks of Otsuka Pharmaceutical Company.
©2020, Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan
For more information about Abilify Mycite go to www.abilifymycite.com or call 1-844-692-4834.

PRINCIPAL DISPLAY PANEL – Kit Carton – 2 mg

30 tablets
Rx only
NDC 59148- 029-85

Abilify MyCite®
(aripiprazole tablets with sensor)

Dispense the accompanying Medication Guide to each patient.

Needs a compatible mobile device.

Please see U.S. FULL PRESCRIBING INFORMATION
including Boxed WARNING enclosed.

Keep Abilify Mycite ® components out of the reach of children.

2 mg

PRINCIPAL DISPLAY PANEL – Kit Carton – 5 mg

30 tablets
Rx only
NDC 59148- 030-85

Abilify MyCite®
(aripiprazole tablets with sensor)

Dispense the accompanying Medication Guide to each patient.

Needs a compatible mobile device.

Please see U.S. FULL PRESCRIBING INFORMATION
including Boxed WARNING enclosed.

Keep Abilify Mycite ® components out of the reach of children.

Swallow tablets whole. Do not divide, crush or chew.

5 mg

PRINCIPAL DISPLAY PANEL – Kit Carton – 10 mg

30 tablets
Rx only
NDC 59148- 031-85

Abilify MyCite®
(aripiprazole tablets with sensor)

Dispense the accompanying Medication Guide to each patient.

Needs a compatible mobile device.

Please see U.S. FULL PRESCRIBING INFORMATION
including Boxed WARNING enclosed.

Keep Abilify Mycite ® components out of the reach of children.

Swallow tablets whole. Do not divide, crush or chew.

10 mg

PRINCIPAL DISPLAY PANEL – Kit Carton – 15 mg

30 tablets
Rx only
NDC 59148- 032-85

Abilify MyCite®
(aripiprazole tablets with sensor)

Dispense the accompanying Medication Guide to each patient.

Needs a compatible mobile device.

Please see U.S. FULL PRESCRIBING INFORMATION
including Boxed WARNING enclosed.

Keep Abilify Mycite ® components out of the reach of children.

Swallow tablets whole. Do not divide, crush or chew.

15 mg

PRINCIPAL DISPLAY PANEL – Kit Carton – 20 mg

30 tablets
Rx only
NDC 59148- 033-85

Abilify MyCite®
(aripiprazole tablets with sensor)

Dispense the accompanying Medication Guide to each patient.

Needs a compatible mobile device.

Please see U.S. FULL PRESCRIBING INFORMATION
including Boxed WARNING enclosed.

Keep Abilify Mycite ® components out of the reach of children.

Swallow tablets whole. Do not divide, crush or chew.

20 mg

PRINCIPAL DISPLAY PANEL – Kit Carton – 30 mg

30 tablets
Rx only
NDC 59148- 034-85

Abilify MyCite®
(aripiprazole tablets with sensor)

Dispense the accompanying Medication Guide to each patient.

Needs a compatible mobile device.

Please see U.S. FULL PRESCRIBING INFORMATION
including Boxed WARNING enclosed.

Keep Abilify Mycite ® components out of the reach of children.

Swallow tablets whole. Do not divide, crush or chew.

30 mg

Abilify Mycite
aripiprazole tablet

معلومات المنتج
نوع المنتجملصق وصف الأدوية البشريةرمز البند (المصدر)NDC:59148-029
مسار الإدارةORALجدول إدارة مكافحة المخدرات
العنصر النشط / النشأة النشطة
اسم العنصرأساس القوةقوة

ARIPIPRAZOLE (ARIPIPRAZOLE)

ARIPIPRAZOLE2 mg
مكونات غير فعالة
اسم العنصرقوة
FERRIC OXIDE RED
FD&C BLUE NO. 2
ALUMINUM OXIDE
ALUMINUM
CUPROUS CHLORIDE
ETHYLCELLULOSE, UNSPECIFIED
GOLD
MAGNESIUM
SILICON
SILICON DIOXIDE
TITANIUM
TRIETHYL CITRATE
STARCH, CORN
HYDROXYPROPYL CELLULOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
FERRIC OXIDE YELLOW
Product Characteristics
اللونgreen (pale green)Scoreno score
ShapeRECTANGLE (modified rectangle)Size8mm
FlavorImprint CodeDA;029;2
Contains
التعبئة والتغليف
#رمز الصنفحزمة الوصف
1NDC:59148-029-851 BOTTLE in 1 KIT
1NDC:59148-029-1330 TABLET in 1 BOTTLE
2NDC:59148-029-901 BOTTLE in 1 CARTON
2NDC:59148-029-0730 TABLET in 1 BOTTLE
المعلومات التسويقية
فئة التسويقرقم الطلب أو الاستشهاد بالدراسةتاريخ بدء التسويقتاريخ انتهاء التسويق
التجمع الوطني الديمقراطيNDA20720201/31/2018

Abilify Mycite
aripiprazole tablet

معلومات المنتج
نوع المنتجملصق وصف الأدوية البشريةرمز البند (المصدر)NDC:59148-030
مسار الإدارةORALجدول إدارة مكافحة المخدرات
العنصر النشط / النشأة النشطة
اسم العنصرأساس القوةقوة

ARIPIPRAZOLE (ARIPIPRAZOLE)

ARIPIPRAZOLE5 mg
مكونات غير فعالة
اسم العنصرقوة
STARCH, CORN
HYDROXYPROPYL CELLULOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
FERRIC OXIDE YELLOW
FERRIC OXIDE RED
FD&C BLUE NO. 2
ALUMINUM OXIDE
ALUMINUM
CUPROUS CHLORIDE
ETHYLCELLULOSE, UNSPECIFIED
GOLD
MAGNESIUM
SILICON
SILICON DIOXIDE
TITANIUM
TRIETHYL CITRATE
Product Characteristics
اللونblue (pale blue)Scoreno score
ShapeRECTANGLE (modified rectangle)Size8mm
FlavorImprint CodeDA;030;5
Contains
التعبئة والتغليف
#رمز الصنفحزمة الوصف
1NDC:59148-030-851 BOTTLE in 1 KIT
1NDC:59148-030-1330 TABLET in 1 BOTTLE
2NDC:59148-030-901 BOTTLE in 1 CARTON
2NDC:59148-030-0730 TABLET in 1 BOTTLE
المعلومات التسويقية
فئة التسويقرقم الطلب أو الاستشهاد بالدراسةتاريخ بدء التسويقتاريخ انتهاء التسويق
التجمع الوطني الديمقراطيNDA20720201/31/2018

Abilify Mycite
aripiprazole tablet

معلومات المنتج
نوع المنتجملصق وصف الأدوية البشريةرمز البند (المصدر)NDC:59148-031
مسار الإدارةORALجدول إدارة مكافحة المخدرات
العنصر النشط / النشأة النشطة
اسم العنصرأساس القوةقوة

ARIPIPRAZOLE (ARIPIPRAZOLE)

ARIPIPRAZOLE10 mg
مكونات غير فعالة
اسم العنصرقوة
STARCH, CORN
HYDROXYPROPYL CELLULOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
FERRIC OXIDE YELLOW
FERRIC OXIDE RED
FD&C BLUE NO. 2
ALUMINUM OXIDE
ALUMINUM
CUPROUS CHLORIDE
ETHYLCELLULOSE, UNSPECIFIED
GOLD
MAGNESIUM
SILICON
SILICON DIOXIDE
TITANIUM
TRIETHYL CITRATE
Product Characteristics
اللونwhite (off-white to pale pink)Scoreno score
ShapeRECTANGLE (modified rectangle)Size8mm
FlavorImprint CodeDA;031;10
Contains
التعبئة والتغليف
#رمز الصنفحزمة الوصف
1NDC:59148-031-851 BOTTLE in 1 KIT
1NDC:59148-031-1330 TABLET in 1 BOTTLE
2NDC:59148-031-901 BOTTLE in 1 CARTON
2NDC:59148-031-0730 TABLET in 1 BOTTLE
المعلومات التسويقية
فئة التسويقرقم الطلب أو الاستشهاد بالدراسةتاريخ بدء التسويقتاريخ انتهاء التسويق
التجمع الوطني الديمقراطيNDA20720201/31/2018

Abilify Mycite
aripiprazole tablet

معلومات المنتج
نوع المنتجملصق وصف الأدوية البشريةرمز البند (المصدر)NDC:59148-032
مسار الإدارةORALجدول إدارة مكافحة المخدرات
العنصر النشط / النشأة النشطة
اسم العنصرأساس القوةقوة

ARIPIPRAZOLE (ARIPIPRAZOLE)

ARIPIPRAZOLE15 mg
مكونات غير فعالة
اسم العنصرقوة
STARCH, CORN
HYDROXYPROPYL CELLULOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
FERRIC OXIDE YELLOW
FERRIC OXIDE RED
FD&C BLUE NO. 2
ALUMINUM OXIDE
ALUMINUM
CUPROUS CHLORIDE
ETHYLCELLULOSE, UNSPECIFIED
GOLD
MAGNESIUM
SILICON
SILICON DIOXIDE
TITANIUM
TRIETHYL CITRATE
Product Characteristics
اللونyellow (pale yellow)Scoreno score
ShapeROUNDSize6mm
FlavorImprint CodeDA;032;15
Contains
التعبئة والتغليف
#رمز الصنفحزمة الوصف
1NDC:59148-032-851 BOTTLE in 1 KIT
1NDC:59148-032-1330 TABLET in 1 BOTTLE
2NDC:59148-032-901 BOTTLE in 1 CARTON
2NDC:59148-032-0730 TABLET in 1 BOTTLE
المعلومات التسويقية
فئة التسويقرقم الطلب أو الاستشهاد بالدراسةتاريخ بدء التسويقتاريخ انتهاء التسويق
التجمع الوطني الديمقراطيNDA20720201/31/2018

Abilify Mycite
aripiprazole tablet

معلومات المنتج
نوع المنتجملصق وصف الأدوية البشريةرمز البند (المصدر)NDC:59148-033
مسار الإدارةORALجدول إدارة مكافحة المخدرات
العنصر النشط / النشأة النشطة
اسم العنصرأساس القوةقوة

ARIPIPRAZOLE (ARIPIPRAZOLE)

ARIPIPRAZOLE20 mg
مكونات غير فعالة
اسم العنصرقوة
STARCH, CORN
HYDROXYPROPYL CELLULOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
FERRIC OXIDE YELLOW
FERRIC OXIDE RED
FD&C BLUE NO. 2
ALUMINUM OXIDE
ALUMINUM
CUPROUS CHLORIDE
ETHYLCELLULOSE, UNSPECIFIED
GOLD
MAGNESIUM
SILICON
SILICON DIOXIDE
TITANIUM
TRIETHYL CITRATE
Product Characteristics
اللونwhite (white to pale yellowish white)Scoreno score
ShapeROUNDSize8mm
FlavorImprint CodeDA;033;20
Contains
التعبئة والتغليف
#رمز الصنفحزمة الوصف
1NDC:59148-033-851 BOTTLE in 1 KIT
1NDC:59148-033-1330 TABLET in 1 BOTTLE
2NDC:59148-033-901 BOTTLE in 1 CARTON
2NDC:59148-033-0730 TABLET in 1 BOTTLE
المعلومات التسويقية
فئة التسويقرقم الطلب أو الاستشهاد بالدراسةتاريخ بدء التسويقتاريخ انتهاء التسويق
التجمع الوطني الديمقراطيNDA20720201/31/2018

Abilify Mycite
aripiprazole tablet

معلومات المنتج
نوع المنتجملصق وصف الأدوية البشريةرمز البند (المصدر)NDC:59148-034
مسار الإدارةORALجدول إدارة مكافحة المخدرات
العنصر النشط / النشأة النشطة
اسم العنصرأساس القوةقوة

ARIPIPRAZOLE (ARIPIPRAZOLE)

ARIPIPRAZOLE30 mg
مكونات غير فعالة
اسم العنصرقوة
STARCH, CORN
HYDROXYPROPYL CELLULOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
FERRIC OXIDE YELLOW
FERRIC OXIDE RED
FD&C BLUE NO. 2
ALUMINUM OXIDE
ALUMINUM
CUPROUS CHLORIDE
ETHYLCELLULOSE, UNSPECIFIED
GOLD
MAGNESIUM
SILICON
SILICON DIOXIDE
TITANIUM
TRIETHYL CITRATE
Product Characteristics
اللونwhite (off-white to pale pink)Scoreno score
ShapeROUNDSize9mm
FlavorImprint CodeDA;034;30
Contains
التعبئة والتغليف
#رمز الصنفحزمة الوصف
1NDC:59148-034-851 BOTTLE in 1 KIT
1NDC:59148-034-1330 TABLET in 1 BOTTLE
2NDC:59148-034-901 BOTTLE in 1 CARTON
2NDC:59148-034-0730 TABLET in 1 BOTTLE
المعلومات التسويقية
فئة التسويقرقم الطلب أو الاستشهاد بالدراسةتاريخ بدء التسويقتاريخ انتهاء التسويق
التجمع الوطني الديمقراطيNDA20720201/31/2018

Labeler – Otsuka America Pharmaceutical, Inc. (008314390)

Otsuka America Pharmaceutical, Inc.

Related questions

.

Leave A Reply

Your email address will not be published.