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نشرة الممارس الصحي نشرة معلومات المريض بالعربية نشرة معلومات المريض بالانجليزية صور الدواء بيانات الدواء
  SFDA PIL (Patient Information Leaflet (PIL) are under review by Saudi Food and Drug Authority)

The name of your medicine is Atacand. The active ingredient is candesartan cilexetil. This belongs to a group of medicines called angiotensin II receptor antagonists. It works by making your blood vessels relax and widen. This helps to lower your blood pressure. It also makes it easier for your heart to pump blood to all parts of your body.
This is medicine is used for:

  •  treating high blood pressure (hypertension) in adult patients.
  •  treating adult heart failure patients with reduced heart muscle function, in addition to Angiotensin Converting Enzyme (ACE) inhibitors or when ACE inhibitors cannot be used (ACE inhibitors are a group of medicines used to treat heart failure).

Do not take Atacand if you are pregnant, think you might be pregnant or considering becoming pregnant. You must tell your doctor if you think you are (or might become) pregnant. Atacand may cause serious harm or even death to your baby if used during pregnancy (see Pregnancy section).

Do not take Atacand

  •  if you are allergic (hypersensitive) to candesartan cilexetil or any of the other ingredients of Atacand (see section 6).
  •  if you are breast-feeding.
  •  if you have severe liver disease or biliary obstruction (a problem with the drainage of the bile from the gall bladder).
  •  If you are taking blood pressure medicine containing aliskiren and you have diabetes mellitus.
  • If you are taking a blood pressure medicine containing aliskiren and you have kidney problems.

If you are not sure if any of these apply to you, talk to your doctor or pharmacist before taking Atacand.

Take special care with Atacand
Before you take, or whilst you are taking Atacand, tell your doctor.

  •  if you have heart, liver or kidney problems, or are on dialysis.
  •  if you have recently had a kidney transplant.
  •  if you are vomiting, have recently had severe vomiting, or have diarrhoea.
  •  if you have a disease of the adrenal gland called Conn’s syndrome (also called primary hyperaldosteronism).
  •  if you have low blood pressure.
  • if you have ever had a stroke.
  • if you are taking any of the following medicines used to treat high blood pressure:

- an “ACE-inhibitor” (for example enalapril, lisinopril, ramipril), in particular if you have diabetes-related kidney problems.
- aliskiren

  •  if you are taking an ACE-inhibitor together with a medicine which belongs to the class of medicines known as mineralocorticoid receptor antagonists (MRA). These medicines are for the treatment of heart failure (see “Other medicines and Atacand”).

Your doctor may want to see you more often and do some tests if you have any of these conditions.
If you are going to have an operation, tell your doctor or dentist that you are taking Atacand. This is because Atacand, when combined with some anaesthetics, may cause a drop in blood pressure.
Use in children
There is no experience with the use of Atacand in children (below the age of 18 years). Therefore Atacand should not be given to children.
Using other medicines
Please tell your doctor or pharmacist if you are using, or have recently used, any other medicines, including medicines obtained without a prescription.
Atacand can affect the way some other medicines work and some medicines can have an effect on Atacand. If you are using certain medicines, your doctor may need to do blood tests from time to time.
In particular, tell your doctor if you are using any of the following medicines:

  •  Other medicines to help lower your blood pressure, including beta-blockers, diazoxide, aliskiren and ACE inhibitors such as enalapril, captopril, lisinopril or ramipril.
  •  Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, diclofenac, celecoxib or etoricoxib (medicines to relieve pain and inflammation).
  •  Acetylsalicylic acid (if you are taking more than 3 g each day) (medicine to relieve pain and inflammation).
  •  Potassium supplements or salt substitutes containing potassium (medicines that increase the amount of potassium in your blood).
  •  Heparin (a medicine for thinning the blood).
  •  Water tablets (diuretics).
  •  Lithium (a medicine for mental health problems).

Taking Atacand with food and drink (in particular alcohol)

  •  You can take Atacand with or without food.
  •  When you are prescribed Atacand, discuss with your doctor before drinking alcohol. Alcohol may make you feel faint or dizzy.

Pregnancy and breast-feeding
Pregnancy

You must not take Atacand if you are pregnant, might be pregnant, or are considering becoming pregnant. You must tell your doctor if you think you are (or might become) pregnant. Your doctor will ask you to stop taking Atacand before you become pregnant or as soon as you know you are pregnant and may recommend another medicine instead of Atacand. Atacand may cause serious harm or even death to your baby if used during pregnancy.
Breast-feeding
Tell your doctor if you are breast-feeding or about to start breast-feeding. Atacand must not be used by mothers who are breast-feeding.
Driving and using machines
Some people may feel tired or dizzy when taking Atacand. If this happens to you, do not drive or use any tools or machines.
Important information about some of the ingredients of Atacand
Atacand contains lactose which is a type of sugar. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.


Always take Atacand exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. It is important to keep taking Atacand every day.

You can take Atacand with or without food.
Swallow the tablet with a drink of water.
Try to take the tablet at the same time each day. This will help you to remember to take it.
High blood pressure:

  •  The usual dose of Atacand is 8 mg once a day. Your doctor may increase this dose to 16 mg once a day and further up to 32 mg once a day depending on blood pressure response.
  •  In some patients, such as those with liver problems, kidney problems or those who recently have lost body fluids, e.g., through vomiting or diarrhoea or by using water tablets, the doctor may prescribe a lower starting dose.
  •  Some black patients may have a reduced response to this type of medicine, when given as the only treatment, and these patients may need a higher dose.

Heart failure:

  •  The usual starting dose of Atacand is 4 mg once a day. Your doctor may increase your dose by doubling the dose at intervals of at least 2 weeks up to 32 mg once a day. Atacand can be taken together with other medicines for heart failure, and your doctor will decide which treatment is suitable for you.

If you take more Atacand than you should
If you take more Atacand than prescribed by your doctor, contact a doctor or pharmacist immediately for advice.

If you forget to take Atacand
Do not take a double dose to make up for a forgotten tablet. Just take the next dose as normal.
If you stop taking Atacand
If you stop taking Atacand, your blood pressure may increase again. Therefore do not stop taking Atacand without first talking to your doctor.
If you have any further questions on the use of this product, ask your doctor or pharmacist.


Like all medicines, Atacand can cause side effects, although not everybody gets them. It is important that you are aware of what these side effects may be.
Stop taking Atacand and seek medical help immediately if you have any of the following allergic reactions:

  •  difficulties in breathing, with or without swelling of the face, lips, tongue and/or throat
  •  swelling of the face, lips, tongue and/or throat, which may cause difficulties in swallowing
  •  severe itching of the skin (with raised lumps)

Atacand may cause a reduction in number of white blood cells. Your resistance to infection may be decreased and you may notice tiredness, an infection or a fever. If this happens contact your doctor. Your doctor may occasionally do blood tests to check whether Atacand has had any effect on your blood (agranulocytosis).
Other possible side effects include:
Common (affects 1 to 10 users in 100)

  •  Feeling dizzy/spinning sensation.
  •  Headache.
  •  Respiratory infection.
  •  Low blood pressure. This may make you feel faint or dizzy.
  •  Changes in blood test results:

- An increased amount of potassium in your blood, especially if you already have kidney problems or heart failure. If this is severe you may notice tiredness, weakness, irregular heart beat or pins and needles.

  •  Effects on how your kidneys work, especially if you already have kidney problems or heart failure. In very rare cases, kidney failure may occur.

Very rare (affects less than 1 user in 10,000)

  •  Swelling of the face, lips, tongue and/or throat.
  •  A reduction in your red or white blood cells. You may notice tiredness, an infection or a fever.
  •  Skin rash, lumpy rash (hives).
  •  Itching.
  •  Back pain, pain in joints and muscles.
  •  Changes in how your liver is working, including inflammation of the liver (hepatitis). You may notice tiredness, yellowing of your skin and the whites of your eyes and flu like symptoms.
  •  Nausea.
  •  Changes in blood test results:

- A reduced amount of sodium in your blood. If this is severe then you may notice weakness, lack of energy, or muscle cramps.

  •  Cough

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.


  •  Keep out of the reach and sight of children.
  • Do not use Atacand after the expiry date which is stated on the carton, blister pack or bottle. The expiry date refers to the last day of that month.
  •  Keep the drug under 30ºC.
  •  Keep the tablets in the original package.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.


  • The active ingredient is candesartan cilexetil. The tablets contain 4 mg, 8 mg, 16 mg or 32 mg of candesartan cilexetil.
  •  The other ingredients are carmellose calcium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, maize starch and macrogol. The 8 mg, 16 mg and 32 mg tablets also contain iron oxide (E172).

4 mg tablets are white, round tablets with a score and marked A/CF on one side and 004 on the other. 8 mg tablets are light pink, round tablets with a score and marked A/CG on one side and 008 on the other. 16 mg tablets are pink, round tablets with a score and marked A/CH on one side and 016 on the other. 32 mg tablets are pink, round tablets with a score and marked A/CL on one side and 032 on the other. The tablet can be divided into equal halves by breaking along the score line. Atacand 4 mg, 8 mg, 16 mg and 32 mg tablets are available in boxes with 28 tablets, conditioned in blister packs with 14 units.

Atacand is manufactured in Sweden by: AstraZeneca AB, SE-151 85 Södertälje,
Sweden
Candesartan cilexetil is manufactured under the licence of:
Takeda Pharmaceutical Company Limited, Japan


June 2015
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

اسم الدواء هو أتاكاند. المادة الفعالة هي كانديسارتان سيليكسيتيل. وهي تنتمي إلى مجموعة الأدوية التي

يطلق عليها مضادات مستقبلات أنجيوتنسين II . وهي تعمل على إرخاء وتوسعة الأوعية الدموية. كما تساعد على

خفض ضغط الدم. وتسهل كذلك من عملية ضخ القلب للدم إلى جميع أجزاء الجسم.

يستخدم هذا الدواء من أجل :

  • علاج ضغط الدم (فرط ضغط الدم) لدى المرضى البالغين.
  •  علاج فشل القلب لدى البالغين المصابين بضعف العضلات إضافة إلى مثبطات الإنزيم المحول للأنجيوتنسين ( ACE ) أو عند تعذر الاستفادة من الإنزيم المحول للأنجيوتنسين (مثبطات الإنزيم المحول للأنجيوتنسين هي مجموعة الأدوية المستخدمة في علاج فشل القلب).

لا تتناولي عقار أتاكاند إذا كنتِ حاملاً أو تعتقدين باحتمالية الحمل أو تنوين أن تكوني حاملاً يجب عليك إخبار الطبيب إذا كنتِ حاملاً أو تعتقدين باحتمالية الحمل. قد يسبب أتاكاند ضررًا كبيرًا أو قد يتسبب في وفاة طفلك عند استخدامه أثناء الحمل (انظري قسم الحمل).

 

لا تتناول عقار أتاكاند

  •  إذا كانت لديك حساسية )فرط حساسية( تجاه كانديسارتان سيليكسيتيل أو أ ي من المكونات الأخرى لأتاكاند (انظر قسم 6 .)
  •  إذا كن تِ ترضعين طبيعيًا.
  •  إذا كنت تعاني من مرض كبدي حاد أو انسداد في الحويصلة الصفراوية (وهي مشكلة في تصريف إفرازات الصفراء من المرارة).
  •  إذا كنت تتناول أدوية ضغط الدم التي تحتوي على أليسكيرين وكان لديك مرض السكري.
  •  إذا كنت تتناول أدوية ضغط الدم التي تحتوي على أليسكيرين وكان لديك مشاكل في الكلى.

إذا كنت غير متأكد من انطباق أي من هذه الحالات، فتحدث إلى طبيبك أو الصيدلي الخاص بك قبل تناول عقار
أتاكاند.

تو خ الحرص الشديد عند تناول عقار أتاكاند
قبل أو أثناء تناول أتاكاند، أخبر طبيبك في حال.

  •  كنت تعاني من مشاكل في الكبد أو الكلى أو القلب أو كنت تقوم بعمليات غسيل كلوي.
  •  خضعت مؤخرًا لعملية زراعة كلى.
  •  كنت تعاني من التقيؤ أو عانيت مؤخرًا من التقيؤ الشديد أو تعاني من الإسهال.
  •  كنت تعاني من مرض الغدة الكظرية المعروف بمتلازمة كون (يعرف أيضًا بفرط الألدوستيرونية الأولي).
  •  كنت تعاني من انخفاض ضغط الدم.
  •  عانيت يومًا من سكتة دماغية.
  •  كنت تتناول أي من الأدوية التالية المستخدمة لعلاج ارتفاع ضغط الدم:

- مثبطات الإنزيم المُحَوِّل للأنجيوتنسين ( ACE )على سبيل المثال: إنالابريل، ليزينوبريل، راميبريل(،
وخصوصاً إذا كانت لديك مشاكل في الكلى المتعلقة بمرض السكري.
- أليسكيرين.

  •  كنت تتناول مثبطات الإنزيم المُحَوِّل للأنجيوتنسين ( ACE ) جنبا إلى جنب مع الدواء الذي ينتمي إلى مجموعة الأدوية المعروفة باسم مضادات مستقبلات مينيرلاكورتيكويد (MRA ). هذه الأدوية لعلاج فشل القلب (راجع القسم "استخدام أدوية أخرى" بالكامل).

قد يرغب طبيبك في الكشف عليك عد ة مرات وإجراء بعض الإختبارات إذا تعرضت للحالات المذكورة أعلاه.
في حالة خضوعك لعملية، فأخبر الطبيب أو طبيب الأسنان أنك تتناول عقار أتاكاند. ويرجع ذلك إلى أن أتاكاند عند
إضافته إلى بعض أنواع عقارات التخدير، قد يسبب انخفاض في ضغط الدم.
الاستخدام لدى الأطفال
لم يتم إجراء أية تجارب على استخدام أتاكاند مع (أقل من 18 عامًا). ومن ثم يجب الامتناع عن إعطاء
عقار أتاكاند للأطفال.
استخدام أدوية أخرى
يرجى أن تخبر طبيبك أو الصيدلي الخاص بك إذا كنت تستخدم أو استخدمت مؤخرًا أي أدوية أخرى بما في ذلك
الأدوية التي حصلت عليها دون وصفة طبية.
يمكن أن يؤثر أتاكاند على طريقة عمل بعض الأدوية الأخرى وقد تؤثر بعض الأدوية الأخرى على عمل عقار
أتاكاند. إذا كنت تستخدم أنواعًا محددة من الأدوية، فقد يكون الطبيب في حاجة إلى إجراء بعض اختبارات الدم
من وقت لآخر.
إذا كنت تستخدم أي من الأدوية التالية بشكل محدد، فأخبر طبيبك :

  •  أدوية أخرى تساعدك على خفض ضغط الدم بما في ذلك حاصرات البيتا وديازوكسيد و اليسكيرين ومثبطات الإنزيم المُحَوِّل للأنجيوتنسين ( ACE ) مثل إنالابريل أو كابتوبريل أو ليزينوبريل أو راميبريل.
  • الأدوية المضادة للالتهاب غير الستيرويدية ( NSAIDs ) مثل إيبوبروفين أو نابروكسين أو ديكلوفيناك أو سيليكوكسيب أو إيتوريكوكسيب (أدوية تؤخذ لتخفيف الألم والالتهاب).
  • حمض الأسيتيل ساليساليك (إذا كنت تتناول أكثر من 3 ملجم يوميًا) (دواء يؤخذ لتخفيف الألم والالتهاب).
  • مكملات البوتاسيوم أو بدائل الملح التي تحتوي على البوتاسيوم (أدوية تزيد من كمية البوتاسيوم في الدم).
  • هيبارين (دواء لزيادة سيولة الدم).
  • أقراص المياه (مدرة للبول).
  • الليثيوم (دواء يعالج مشاكل الصحة العقلية).

تناول أتاكاند مع الطعام والشراب (الكحول بشكل خاص)

  •  يمكنك تناول أتاكاند مع الطعام أو بدونه.
  •  عند وصف أتاكاند لك، ناقش الأمر مع الطبيب قبل احتساء الكحول. قد يؤدي احتساء الكحول إلى شعورك بالضعف أو الدوار.

الحمل والرضاعة
الحمل

يجب تجنب تناول أتاكاند إذا كن تِ حاملاً أو تعتقدين باحتمالية الحمل أو تنوين أن تكوني حاملاً. يجب عليك إخبار
الطبيب إذا كنتِ حاملاً أو تعتقدين باحتمالية الحمل. سيطلب منك الطبيب التوقف عن تناول عقار أتاكاند قبل
الحمل أو بمجرد العلم بالحمل وقد يوصي ببعض الأدوية الأخرى بد لا من أتاكاند. قد يسبب أتاكاند ضررًا كبيرًا أو
قد يتسبب في وفاة طفلك عند استخدامه أثناء الحمل.

الرضاعة
أخبري الطبيب إذا كنتِ تقومين بالرضاعة أو على وشك بدء الرضاعة. يجب تجنب استخدام أتاكاند من جانب
الأمهات اللاتي يرضعن طبيعيًا.
القيادة واستخدام الآلات
قد يشعر بعض الأشخاص بالتعب أو الدوار عند تناول عقار أتاكاند. وإذا ما حدث هذا لك، فلا تقم بالقيادة أو
تستخدم أية أدوات أو آلات.
معلومات مهمة حول بعض مكونات عقار أتاكاند
يحتوي عقار أتاكاند على اللاكتوز وهو أحد أنواع السكر. إذا أخبرك الطبيب أن ك لا تحتمل بعض أنواع السكر،
فعليك الاتصال به قبل تناول هذا الدواء.

https://localhost:44358/Dashboard

عليك تناول أتاكاند دومًا وفقًا لتوجيهات الطبيب. يتعي ن عليك مراجعة طبيبك أو الصيدلي الخاص بك إذا لم تكن

متأك دًا. من الهام الالتزام بتناول أتاكاند يوميًا.

يمكنك تناول أتاكاند مع الطعام أو بدونه.

ابتلع القرص مع شربة ماء.

تناول القرص في الوقت نفسه يوميًا. سيساعدك ذلك على تذكر تناوله.

ضغط الدم المرتفع :

  •  الجرعة الاعتيادية من أتاكاند هي 8 ملجم يوميًا. قد يُزيد الطبيب هذه الجرعة إلى 16 ملجم يوميًا ثم إلى 32 ملجم يوميًا وفق استجابة ضغط الدم.
  • قد يصف الطبيب جرعة بدء أقل لبعض المرضى الذين يعانون من مشاكل في الكبد أو الكلى أو من فقدوا مؤخرًا سوائل الجسم مث لا عبر التقيؤ أو الإسهال أو عبر استخدام أدوية مدر ة للبول.
  • قد تكون استجابة بعض المرضى السود لهذا النوع من الدواء ضعيفة خاصة إذا كان منفردًا وقد يكونوا في حاجة إلى جرعة أكبر.

فشل القلب :

  •  جرعة البداية الاعتيادية من أتاكاند هي 4 ملجم يوميًا. قد يزيد الطبيب جرعتك عبر مضاعفة الجرعة على فترات لا تقل عن أسبوعين لتصل إلى 32 ملجم يوميًا. يمكنك تناول أتاكاند مع أدوية أخرى لفشل القلب وسيقرر الطبيب العلاج المناسب لك.

إذا تناولت جرعة من أتاكاند أكثر مما ينبغي
إذا تناولت جرعة أتاكاند أكثر من الموصوف بمعرفة الطبيب، فاتصل على الطبيب أو الصيدلي على الفور طلبًا للنصيحة.
إذا نسيت تناول أتاكاند
لا تتناول جرعة مزدوجة لتعويض جرعة فائتة. فقط تناول الجرعة التالية كالمعتاد.
إذا توقفت عن تناول أتاكاند
إذا توقفت عن تناول أتاكاند، فقد يزيد ضغط الدم مرة أخرى. ومن ثم لا تتوقف عن تناول أتاكاند من دون إخبار الطبيب أو لا.ً
إذا كانت لديك أي أسئلة أخرى حول استخدام هذا المنتج، فتحدث إلى طبيبك أو الصيدلي.

كما هو الحال في جميع الأدوية ، يمكن أن يتسب ب أتاكاند في حدوث آثار جانبية على الرغم من أنها لا تصيب

جميع المستخدمين. من الهام معرفة طبيعة تلك الآثار الجانبية.

توقف عن تناول أتاكاند واطلب المساعدة الطبية على الفور إذا لاحظت وجود أ ي من التفاعلات التحسسية التالية :

  •  صعوبات في التنفس سواء تورم الوجه و/أو الشفتان و/أو اللسان و/أو الحلق أم لا
  •  تورم الوجه و/أو الشفتان و/أو اللسان و/أو الحلق الذي قد يسبب صعوبات في البلع
  •  حكة جلدية شديدة (مصحوبة ببثور مرتفعة)

قد يسبب أتاكاند انخفاض عدد كريات الدم. قد تقل مقاومة العدوى لديك وقد تشعر بتعب أو عدوى أو حمى.

وإذا حدث ذلك فاتصل على الطبيب. قد يقوم الطبيب من حين لآخر بإجراء بعض اختبارات الدم للتحقق من آثار

أتاكاند على الدم (ندرة المحببات).

تشمل الآثار الجانبية المحتملة الأخرى ما يلي :

شائعة (تؤث ر في عدد يتراوح بين مستخدم إلى عشرة مستخدمين من أصل 100 )

  •  الشعور بالدوخة/الدوار.
  •  الصداع.
  •  عدوى الجهاز التنفسي.
  •  انخفاض ضغط الدم. قد يؤدي هذا إلى شعورك بالضعف أو الدوار.
  •  تغيرات في نتائج اختبار الدم :

- زيادة كمية البوتاسيوم في الدم بشكل خاص إذا كنت تعاني من مشاكل في الكُلى أو فشل القلب.

إذا كان الأمر شديدًا، فقد تشعر بالتعب أو الضعف أو عدم انتظام ضربات القلب أو وخز مثل

الدبابيس والإبر.

  •  تأثيرات على طريقة عمل الكلى بشكل خاص إذا كنت تعاني من مشاكل في الكُلى أو فشل القلب. في حالات نادرة جدًا، قد يحدث فشل كلوي.

نادرة جدًا (تؤثر في أقل من مستخدم في كل 10000 )

  •  تورم الوجه و/أو الشفتان و/أو اللسان و/أو الحلق.
  •  انخفاض في خلايا الدم البيضاء أو الحمراء. قد تشعر بتعب أو عدوى أو حمى.
  •  طفح جلدي، طفح جلدي كتلي (الشرى).
  •  الحكة.
  •  ألم في الظهر وألم في المفاصل والعضلات.
  •  تغيرات على طريقة عمل الكبد بما في ذلك التهاب الكبد (الالتهاب الكبدي). قد تشعر بتعب واصفرار الجلد وبياض العين وأعراض تشبه أعراض الأنفلونزا.
  •  الغثيان.
  •  تغيرات في نتائج اختبار الدم :

- انخفاض نسبة الصوديوم في الدم. إذا كان ذلك شديدًا، فقد تشعر بالتعب أو نقص الطاقة
بشكل عام أو تشنجات عضلية.

  •  السعال

إذا ازدادت خطورة أي من الآثار الجانبية، أو إذا لاحظت ظهور أي آثار جانبية غير مذكورة في هذه النشرة،
فيُرجى إعلام طبيبك أو الصيدلي الخاص بك.

  •  احفظ العقار بعيدًا عن متناول الأطفال ورؤيتهم.
  •  لا تستخدم أتاكاند بعد تاريخ انتهاء صلاحيته المدون على العلبة الخارجية أو الشريط أو الزجاجة الداخلية.

يشير تاريخ انتهاء الصلاحية إلى آخر يوم في الشهر المدو ن.

  •  يُحفظ العقار في درجة حرارة أقل من 3٠ درجة مئوية.
  •  تُحفظ الأقراص في العبوة الأصلية.

 

لا تتخلص من الأدوية عبر مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي الخاص بك عن كيفية
التخلص من الأدوية التي لم تعد تحتاج إليها. حيث تساعد هذه الإجراءات في حماية البيئة.

  •  المادة الفعالة هي كانديسارتان سيليكسيتيل. تحتوي الأقراص على 4 ملجم أو 8 ملجم أو 16 ملجم أو 32 ملجم من كانديسارتان سيليكسيتيل.
  •  المكونات الأخرى هي كالسيوم كارميلوز وهيدروكسي بروبيل سليلوز ومونوهيدرات اللاكتوز وستيارات الماغنسيوم ونشا الذرة وماكروجول. تحتوي أقراص 8 ملجم و 16 ملجم و 32 ملجم كذلك على أكسيد الحديد ) E172
أقراص 4 ملجم ذات لون أبيض ومستديرة بخط محفور في المنتصف ومكتوب عليها A/CF على أحد جانبيها و ٠٠4 على الجانب الآخر. أقراص 8 ملجم ذات لون وردي خفيف ومستديرة بخط محفور في المنتصف ومكتوب عليها A/CG على أحد جانبيها و ٠٠8 على الجانب الآخر. أقراص 16 ملجم ذات لون وردي ومستديرة بخط محفور في المنتصف ومكتوب عليها على أحد A/CH جانبيها و ٠16 على الجانب الآخر. أقراص 32 ملجم ذات لون وردي ومستديرة بخط محفور في المنتصف ومكتوب عليها على أحد A/CL جانبيها و ٠32 على الجانب الآخر. يمكن تقسيم القرص إلى نصفين متساويين بكسره على امتداد الخط المحفور على جانبيه. تتوفر أقراص أتاكاند 4 ملجم و 8 ملجم و 16 ملجم و 32 ملجم في عبوات تحتوي على 28 قرصًا موضوعة في شريطين تحتوي على 14 قرصاً لكل منها.

أتاكاند مصنوع في السويد بواسطة: AstraZeneca AB, SE-151 85 Södertälje, Sweden

يُصنع كانديسارتان سيليكسيتيل بموجب ترخيص من:
المحدودة، اليابان Takeda Pharmaceutical شركة

يونيو 2015
 Read this leaflet carefully before you start using this product as it contains important information for you

Atacand 4 mg tablets Atacand 8 mg tablets Atacand 16 mg tablets Atacand 32 mg tablets

4 mg: Each tablet contains 4 mg candesartan cilexetil 8 mg: Each tablet contains 8 mg candesartan cilexetil 16 mg: Each tablet contains 16 mg candesartan cilexetil 32 mg: Each tablet contains 32 mg candesartan cilexetil Excipient: 4 mg: Each tablet contains 93.4 mg lactose monohydrate 8 mg: Each tablet contains 89.4 mg lactose monohydrate 16 mg: Each tablet contains 81.4 mg lactose monohydrate 32 mg: Each tablet contains 163 mg lactose monohydrate For a full list of excipients, see section 6.1

Tablet 4 mg: Round (diameter 7 mm), white tablets with a score and marked A/CF on one side and marked 004 on the other side. 8 mg: Round (diameter 7 mm), light pink tablets with a score and marked A/CG on one side and marked 008 on the other side. 16 mg: Round (diameter 7 mm), pink tablets with a score and marked A/CH on one side and marked 016 on the other side. 32 mg: Round (diameter 9.5 mm), pink tablets with a score and marked A/CL on one side and marked 032 on the other side. The tablet can be divided into equal halves.

Atacand is indicated for the:

  •  Treatment of essential hypertension in adults.
  •  Treatment of patients with heart failure and impaired left ventricular systolic function (left ventricular ejection fraction ≤ 40%) when Angiotensin Converting Enzyme (ACE) inhibitors are not tolerated or as add-on therapy to ACE-inhibitors in patients with symptomatic heart failure, despite optimal therapy, when mineralocorticoid receptor antagonists are not tolerated (see sections Posology and method of administration, Special warnings and precautions for use, Interactions and Pharmacodynamic properties).

Posology in Hypertension
The recommended initial dose and usual maintenance dose of Atacand is 8 mg once daily. Most of the antihypertensive effect is attained within 4 weeks. In some patients whose blood pressure is not adequately controlled, the dose can be increased to 16 mg once daily and to a maximum of 32 mg once daily.
Atacand may also be administered with other antihypertensive agents (see sections Contraindications, Special warnings and precautions for use, Interactions and Pharmacodynamic properties). Addition of hydrochlorothiazide has been shown to have an additive antihypertensive effect with various doses of Atacand.
Elderly population
No initial dose adjustment is necessary in elderly patients.
Patients with intravascular volume depletion
An initial dose of 4 mg may be considered in patients at risk for hypotension, such as patients with possible volume depletion (see section 4.4).
Patients with renal impairment
No initial dosage adjustment is necessary in patients with mild to moderate renal impairment (i.e. creatinine clearance >30-80 ml/min/1.73 m2 BSA). In patients with severe renal impairment (i.e. creatinine clearance <30 ml/min/1.73 m2 BSA), the clinical experience is limited and a lower initial dose of 4 mg should be considered.
Patients with hepatic impairment

Patients with hepatic impairment: Dose titration is recommended in patients with mild to moderate chronic liver disease, and a lower initial dose of 4 mg should be considered. Atacand should not be used in patients with severe hepatic impairment and/or cholestasis (see sections 4.3).
Black patients
The antihypertensive effect of candesartan is less pronounced in black patients than in non-black patients. Consequently, uptitration of Atacand and concomitant therapy may be more frequently needed for blood pressure control in black patients than in non-black patients (see section 5.1).

Posology in Heart Failure
The usual recommended initial dose of Atacand is 4 mg once daily. Up-titration to the target dose of 32 mg once daily or the highest tolerated dose is done by doubling the dose at intervals of at least 2 weeks (see section 4.4). Atacand may be co-administered with an ACE-inhibitor in patients with symptomatic heart failure despite optimal standard heart failure therapy when mineralocorticoid receptor antagonists are not tolerated.
Concomitant therapy
Atacand can be administered with other heart failure treatment, including ACE inhibitors, beta-blockers, diuretics and digitalis or a combination of these medicinal products (see Special warnings and precautions for use and Pharmacodynamic properties).
Special patient populations
No initial dose adjustment is necessary for elderly patients or in patients with intravascular volume depletion or renal impairment or mild to moderate hepatic impairment.
Paediatric Population
The safety and efficacy of Atacand in children aged between birth and 18 years have not been established in the treatment of hypertension and heart failure. No data are available.
Method of administration
Oral use.
Atacand should be taken once daily with or without food.
The bioavailability of candesartan is not affected by food.


 Hypersensitivity to any component of Atacand.  Pregnancy and lactation (see section 4.6 Pregnancy and lactation).  Severe hepatic impairment and/or cholestasis.  The concomitant use of Atacand with aliskiren-containing products is contraindicated in patients with diabetes mellitus (type I or II) or renal impairment (GFR< 60 ml/min/1.73m2) (see section 4.4 and 4.5).

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see Interactions and Pharmacodynamic properties).

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes, and blood pressure.
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Concomitant therapy with an ACE- inhibitor in heart failure
The risk of adverse events, especially hypotension, hyperkalaemia and decreased renal function (including acute renal failure) may increase when candesartan is used in combination with an ACE inhibitor. Triple combination of an ACE-inhibitor, a mineralocorticoid receptor antagonist and candesartan is also not recommended. Use of these combinations should be under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Renal impairment
As with other agents inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible patients treated with Atacand.
When Atacand is used in hypertensive patients with renal impairment, periodic monitoring of serum potassium and creatinine levels is recommended. There is limited experience in patients with very severe or end-stage renal impairment (Clcreatinine < 15 ml/min). In these patients Atacand should be carefully titrated with thorough monitoring of blood pressure.
Evaluation of patients with heart failure should include periodic assessments of renal function, especially in elderly patients 75 years or older, and patients with impaired renal function. During dose titration of Atacand, monitoring of serum creatinine and potassium is recommended. Clinical trials in heart failure did not include patients with serum creatinine > 265 mol/l (> 3 mg/dl).
Concomitant therapy with an ACE inhibitor in heart failure
The risk of adverse reactions, especially renal function impairment and hyperkalaemia, may increase when Atacand is used in combination with an ACE inhibitor (see section 4.8). Patients with such treatment should be monitored regularly and carefully.
Haemodialysis
During dialysis the blood pressure may be particularly sensitive to AT1-receptor blockade as a result of reduced plasma volume and activation of the renin-angiotensin-aldosterone system. Therefore, Atacand should be carefully titrated with thorough monitoring of blood pressure in patients on haemodialysis.
Renal artery stenosis
Medicinal products that affect the renin-angiotensin-aldosterone system, including angiotensin II receptor antagonists (AIIRAs), may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.
Kidney transplantation
There is limited clinical evidence regarding Atacand use in patients who have undergone renal transplant.
Hypotension
Hypotension may occur during treatment with Atacand in heart failure patients. It may also occur in hypertensive patients with intravascular volume depletion such as those receiving high dose diuretics.

Caution should be observed when initiating therapy and correction of hypovolemia should be attempted.
Anaesthesia and surgery
Hypotension may occur during anaesthesia and surgery in patients treated with angiotensin II antagonists due to blockade of the renin-angiotensin system. Very rarely, hypotension may be severe such that it may warrant the use of intravenous fluids and/or vasopressors.
Aortic and mitral valve stenosis (obstructive hypertrophic cardiomyopathy)
As with other vasodilators, special caution is indicated in patients suffering from haemodynamically relevant aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism will not generally respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin-aldosterone system. Therefore, the use of Atacand is not recommended in this population.
Hyperkalaemia
Concomitant use of Atacand with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (e.g. heparin) may lead to increases in serum potassium in hypertensive patients. Monitoring of potassium should be undertaken as appropriate.
In heart failure patients treated with Atacand, hyperkalaemia may occur. Periodic monitoring of serum potassium is recommended. The combination of an ACE inhibitor, a potassium-sparing diuretic (e.g. spironolactone) and Atacand is not recommended and should be considered only after careful evaluation of the potential benefits and risks.
General
In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other medicinal products that affect this system has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. The possibility of similar effects cannot be excluded with AIIRAs. As with any antihypertensive agent, excessive blood pressure decrease in patients with ischaemic cardiopathy or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke.
The antihypertensive effect of candesartan may be enhanced by other medicinal products with blood pressure lowering properties, whether prescribed as an antihypertensive or prescribed for other indications.
Atacand contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Pregnancy and Lactation
AIIRAs should not be initiated during pregnancy. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).


The combination of candesartan cilexetil with aliskiren-containing medicine is contraindicated in patients with diabetes mellitus (type I or II) or moderate to severe renal impairment (GFR< 60 ml/min/1.73m2) and is not recommended in other patients (see sections Contraindications and Special warnings and precautions for use).
Clinical trial data has shown that dual blockade of the renin angiotensin-aldosterone system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see contraindications, Special warnings and precaution for use, Pharmacodynamic properties).
In patients without heart failure, especially those with kidney problems, candesartan cilexetil should not be used together with ACE inhibitors because of the increased risk of hypotension, hyperkalemia and worsening of renal function.
Compounds which have been investigated in clinical pharmacokinetic studies include hydrochlorothiazide, warfarin, digoxin, oral contraceptives (i.e. ethinylestradiol/levonorgestrel), glibenclamide, nifedipine and enalapril. No clinically significant pharmacokinetic interactions with these medicinal products have been identified.
Concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products (e.g. heparin) may increase potassium levels. Monitoring of potassium should be undertaken as appropriate (see section 4.4).
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. A similar effect may occur with AIIRAs. Use of candesartan with lithium is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.
When AIIRAs are administered simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs) (i.e. selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect may occur.
As with ACE inhibitors, concomitant use of AIIRAs and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.


Use in pregnancy

The use of Atacand is contraindicated during pregnancy (see section 4.3 Contraindications). Patients receiving Atacand should be made aware of that before contemplating a possibility of becoming pregnant so that they can discuss appropriate options with their treating physician. When pregnancy is diagnosed, treatment with Atacand must be stopped immediately and if appropriate, alternative therapy should be started.
When used in pregnancy, drugs that act directly on the renin-angiotensin system can cause foetal and neonatal injury and death. Exposure to angiotensin II receptor antagonist therapy is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).
Use in lactation

It is not known whether candesartan is excreted in human milk. However, candesartan is excreted in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, breast feeding should be discontinued if the use of Atacand is considered essential (see section 4.3 Contra-indications).


No studies on the effects of candesartan on the ability to drive and use machines have been performed. However, it should be taken into account that occasionally dizziness or weariness may occur during treatment with Atacand.


Treatment of Hypertension
In controlled clinical studies adverse reactions were mild and transient. The overall incidence of adverse events showed no association with dose or age. Withdrawals from treatment due to adverse events were similar with candesartan cilexetil (3.1%) and placebo (3.2%).
In a pooled analysis of clinical trial data of hypertensive patients, adverse reactions with candesartan cilexetil were defined based on an incidence of adverse events with candesartan cilexetil at least 1% higher than the incidence seen with placebo. By this definition, the most commonly reported adverse reactions were dizziness/vertigo, headache and respiratory infection.
The table below presents adverse reactions from clinical trials and post-marketing experience.
The frequencies used in the tables throughout section 4.8 are: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000).

 

Laboratory findings
In general, there were no clinically important influences of Atacand on routine laboratory variables. As for other inhibitors of the renin-angiotensin-aldosterone system, small decreases in haemoglobin have been seen. No routine monitoring of laboratory variables is usually necessary for patients receiving Atacand. However, in patients with renal impairment, periodic monitoring of serum potassium and creatinine levels is recommended.
Treatment of Heart Failure

The adverse experience profile of Atacand in heart failure patients was consistent with the pharmacology of the drug and the health status of the patients. In the CHARM clinical programme, comparing Atacand in doses up to 32 mg (n=3,803) to placebo (n=3,796), 21.0% of the candesartan cilexetil group and 16.1% of the placebo group discontinued treatment because of adverse events. The most commonly reported adverse reactions were hyperkalaemia, hypotension and renal impairment. These events were more common in patients over 70 years of age, diabetics, or subjects who received other medicinal products which affect the renin-angiotensin-aldosterone system, in particular an ACE inhibitor and/or spironolactone.
The table below presents adverse reactions from clinical trials and post-marketing experience.

Laboratory findings
Hyperkalaemia and renal impairment are common in patients treated with Atacand for the indication of heart failure. Periodic monitoring of serum creatinine and potassium is recommended (see section 4.4).
To report any side effect(s):
 Saudi Arabia:

The National Pharmacovigilance and Drug Safety Centre (NPC)
o Fax: +966-11-205-7662
o Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
o Toll free phone: 8002490000
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc

Other GCC states:

Please contact the relevant competent authority.


Symptoms
Based on pharmacological considerations, the main manifestation of an overdose is likely to be symptomatic hypotension and dizziness. In individual case reports of overdose (of up to 672 mg candesartan cilexetil) patient recovery was uneventful.
Management
If symptomatic hypotension should occur, symptomatic treatment should be instituted and vital signs monitored. The patient should be placed supine with the legs elevated. If this is not sufficient, plasma volume should be increased by infusion of, for example, isotonic saline solution. Sympathomimetic medicinal products may be administered if the above-mentioned measures are not sufficient.
Candesartan cannot be removed by haemodialysis.


Pharmacotherapeutic group:
Angiotensin II antagonists, plain, ATC code: C09CA06
Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system and plays a role in the pathophysiology of hypertension, heart failure and other cardiovascular disorders. It also has a role in the pathogenesis of end organ hypertrophy and damage. The major physiological effects of angiotensin II, such as vasoconstriction, aldosterone stimulation, regulation of salt and water homeostasis and stimulation of cell growth, are mediated via the type 1 (AT1) receptor.
Candesartan cilexetil is a prodrug suitable for oral use. It is rapidly converted to the active substance, candesartan, by ester hydrolysis during absorption from the gastrointestinal tract. Candesartan is an AIIRA, selective for AT1 receptors, with tight binding to and slow dissociation from the receptor. It has no agonist activity.
Candesartan does not inhibit ACE, which converts angiotensin I to angiotensin II and degrades bradykinin. There is no effect on ACE and no potentiation of bradykinin or substance P. In controlled clinical trials comparing candesartan with ACE inhibitors, the incidence of cough was lower in patients receiving candesartan cilexetil. Candesartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. The antagonism of the angiotensin II (AT1) receptors results in dose related increases in plasma renin levels, angiotensin I and angiotensin II levels, and a decrease in plasma aldosterone concentration.
Hypertension
Two large randomised, controlled trials (ONTARGET (Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of combination of an ACE-inhibitor with an angiotensin II receptor blocker.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.

These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared to monotherapy was observed. Given their similar Pharmacodynamic properties, these results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers.
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in patients with diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the placebo group.
In hypertension, candesartan causes a dose-dependent, long-lasting reduction in arterial blood pressure. The antihypertensive action is due to decreased systemic peripheral resistance, without reflex increase in heart rate. There is no indication of serious or exaggerated first dose hypotension or rebound effect after cessation of treatment.
After administration of a single dose of candesartan cilexetil, onset of antihypertensive effect generally occurs within 2 hours. With continuous treatment, most of the reduction in blood pressure with any dose is generally attained within four weeks and is sustained during long-term treatment. According to a meta-analysis, the average additional effect of a dose increase from 16 mg to 32 mg once daily was small. Taking into account the inter-individual variability, a more than average effect can be expected in some patients. Candesartan cilexetil once daily provides effective and smooth blood pressure reduction over 24 hours, with little difference between maximum and trough effects during the dosing interval. The antihypertensive effect and tolerability of candesartan and losartan were compared in two randomised, double-blind studies in a total of 1,268 patients with mild to moderate hypertension. The trough blood pressure reduction (systolic/diastolic) was 13.1/10.5 mmHg with candesartan cilexetil 32 mg once daily and 10.0/8.7 mmHg with losartan potassium 100 mg once daily (difference in blood pressure reduction 3.1/1.8 mmHg, p<0.0001/p<0.0001).
When candesartan cilexetil is used together with hydrochlorothiazide, the reduction in blood pressure is additive. An increased antihypertensive effect is also seen when candesartan cilexetil is combined with amlodipine or felodipine.
Medicinal products that block the renin-angiotensin-aldosterone system have less pronounced antihypertensive effect in black patients (usually a low-renin population) than in non-black patients. This is also the case for candesartan. In an open label clinical experience trial in 5,156 patients with diastolic hypertension, the blood pressure reduction during candesartan treatment was significantly less in black than non-black patients (14.4/10.3 mmHg vs 19.0/12.7 mmHg, p<0.0001/p<0.0001).
Candesartan increases renal blood flow and either has no effect on or increases glomerular filtration rate while renal vascular resistance and filtration fraction are reduced. In a 3-month clinical study in hypertensive patients with type 2 diabetes mellitus and microalbuminuria, antihypertensive treatment with candesartan cilexetil reduced urinary albumin excretion (albumin/creatinine ratio, mean 30%, 95%CI 15-42%). There is currently no data on the effect of candesartan on the progression to diabetic nephropathy.
The effects of candesartan cilexetil 8-16 mg (mean dose 12 mg), once daily, on cardiovascular morbidity and mortality were evaluated in a randomised clinical trial with 4,937 elderly patients (aged 70-89 years; 21% aged 80 or above) with mild to moderate hypertension followed for a mean of 3.7 years (Study on COgnition and Prognosis in the Elderly). Patients received candesartan cilexetil or placebo with other antihypertensive treatment added as needed. The blood pressure was reduced from 166/90 to 145/80 mmHg in the candesartan group, and from 167/90 to 149/82 mmHg in the control group. There was no statistically significant difference in the primary endpoint, major cardiovascular events (cardiovascular mortality, non-fatal stroke and non-fatal myocardial infarction). There were 26.7 events per 1000 patient-years in the candesartan group versus 30.0 events per 1000 patient-years in the control group (relative risk 0.89, 95%CI 0.75 to 1.06, p=0.19).

Heart Failure
Treatment with candesartan cilexetil reduces mortality, reduces hospitalisation due to heart failure, and improves symptoms in patients with left ventricular systolic dysfunction as shown in the Candesartan in Heart failure – Assessment of Reduction in Mortality and morbidity (CHARM) programme.
This placebo controlled, double-blind study programme in chronic heart failure (CHF) patients with NYHA functional class II to IV consisted of three separate studies: CHARM-Alternative (n=2,028) in patients with LVEF  40% not treated with an ACE inhibitor because of intolerance (mainly due to cough, 72%), CHARM-Added (n=2,548) in patients with LVEF  40% and treated with an ACE inhibitor, and CHARM-Preserved (n=3,023) in patients with LVEF > 40%. Patients on optimal CHF therapy at baseline were randomised to placebo or candesartan cilexetil (titrated from 4 mg or 8 mg once daily to 32 mg once daily or the highest tolerated dose, mean dose 24 mg) and followed for a median of 37.7 months. After 6 months of treatment 63% of the patients still taking candesartan cilexetil (89%) were at the target dose of 32 mg.
In CHARM-Alternative, the composite endpoint of cardiovascular mortality or first CHF hospitalisation was significantly reduced with candesartan in comparison with placebo, hazard ratio (HR) 0.77 (95%CI: 0.67 to 0.89, p< 0.001). This corresponds to a relative risk reduction of 23%. Of candesartan patients 33.0% (95%CI: 30.1 to 36.0) and of placebo patients 40.0% (95%CI: 37.0 to 43.1) experienced this endpoint, absolute difference 7.0% (95%CI: 11.2 to 2.8). Fourteen patients needed to be treated for the duration of the study to prevent one patient from dying of a cardiovascular event or being hospitalised for treatment of heart failure. The composite endpoint of all-cause mortality or first CHF hospitalisation was also significantly reduced with candesartan, HR 0.80 (95%CI: 0.70 to 0.92, p=0.001). Of candesartan patients 36.6% (95%CI: 33.7 to 39.7) and of placebo patients 42.7% (95%CI: 39.6 to 45.8) experienced this endpoint, absolute difference 6.0% (95%CI: 10.3 to 1.8). Both the mortality and morbidity (CHF hospitalisation) components of these composite endpoints contributed to the favourable effects of candesartan. Treatment with candesartan cilexetil resulted in improved NYHA functional class (p=0.008).
In CHARM-Added, the composite endpoint of cardiovascular mortality or first CHF hospitalisation was significantly reduced with candesartan in comparison with placebo, HR 0.85 (95%CI: 0.75 to 0.96, p=0.011). This corresponds to a relative risk reduction of 15%. Of candesartan patients 37.9% (95%CI: 35.2 to 40.6) and of placebo patients 42.3% (95%CI: 39.6 to 45.1) experienced this endpoint, absolute difference 4.4% (95%CI: 8.2 to 0.6). Twenty-three patients needed to be treated for the duration of the study to prevent one patient from dying of a cardiovascular event or being hospitalised for treatment of heart failure. The composite endpoint of all-cause mortality or first CHF hospitalisation was also significantly reduced with candesartan, HR 0.87 (95%CI: 0.78 to 0.98, p=0.021). Of candesartan patients 42.2% (95%CI: 39.5 to 45.0) and of placebo patients 46.1% (95%CI: 43.4 to 48.9) experienced this endpoint, absolute difference 3.9% (95%CI: 7.8 to 0.1). Both the mortality and morbidity components of these composite endpoints contributed to the favourable effects of candesartan. Treatment with candesartan cilexetil resulted in improved NYHA functional class (p=0.020).
In CHARM-Preserved, no statistically significant reduction was achieved in the composite endpoint of cardiovascular mortality or first CHF hospitalisation, HR 0.89 (95%CI: 0.77 to 1.03, p=0.118).
All-cause mortality was not statistically significant when examined separately in each of the three CHARM studies. However, all-cause mortality was also assessed in pooled populations, CHARM- Alternative and CHARM-Added, HR 0.88 (95%CI: 0.79 to 0.98, p=0.018) and all three studies, HR 0.91 (95%CI: 0.83 to 1.00, p=0.055).
The beneficial effects of candesartan were consistent irrespective of age, gender and concomitant medication. Candesartan was effective also in patients taking both beta-blockers and ACE inhibitors at the same time, and the benefit was obtained whether or not patients were taking ACE inhibitors at the target dose recommended by treatment guidelines.
In patients with CHF and depressed left ventricular systolic function (left ventricular ejection fraction, LVEF  40%), candesartan decreases systemic vascular resistance and pulmonary capillary wedge pressure, increases plasma renin activity and angiotensin II concentration, and decreases aldosterone levels.


Absorption and distribution
Following oral administration, candesartan cilexetil is converted to the active substance candesartan. The absolute bioavailability of candesartan is approximately 40% after an oral solution of candesartan cilexetil. The relative bioavailability of the tablet formulation compared with the same oral solution is approximately 34% with very little variability. The estimated absolute bioavailability of the tablet is therefore 14%. The mean peak serum concentration (Cmax) is reached 3-4 hours following tablet intake. The candesartan serum concentrations increase linearly with increasing doses in the therapeutic dose range. No gender related differences in the pharmacokinetics of candesartan have been observed. The area under the serum concentration versus time curve (AUC) of candesartan is not significantly affected by food.
Candesartan is highly bound to plasma protein (more than 99%). The apparent volume of distribution of candesartan is 0.1 l/kg.
The bioavailability of candesartan is not affected by food.

Biotransformation and elimination
Candesartan is mainly eliminated unchanged via urine and bile and only to a minor extent eliminated by hepatic metabolism (CYP2C9). Available interaction studies indicate no effect on CYP2C9 and CYP3A4. Based on in vitro data, no interaction would be expected to occur in vivo with drugs whose metabolism is dependent upon cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4. The terminal half-life of candesartan is approximately 9 hours. There is no accumulation following multiple doses.
Total plasma clearance of candesartan is about 0.37 ml/min/kg, with a renal clearance of about 0.19 ml/min/kg. The renal elimination of candesartan is both by glomerular filtration and active tubular secretion. Following an oral dose of 14C-labelled candesartan cilexetil, approximately 26% of the dose is excreted in the urine as candesartan and 7% as an inactive metabolite while approximately 56% of the dose is recovered in the faeces as candesartan and 10% as the inactive metabolite.
Pharmacokinetics in special populations
In the elderly (over 65 years) Cmax and AUC of candesartan are increased by approximately 50% and 80%, respectively in comparison to young subjects. However, the blood pressure response and the incidence of adverse events are similar after a given dose of Atacand in young and elderly patients (see section 4.2).

In patients with mild to moderate renal impairment Cmax and AUC of candesartan increased during repeated dosing by approximately 50% and 70%, respectively, but t½ was not altered, compared to patients with normal renal function. The corresponding changes in patients with severe renal impairment were approximately 50% and 110%, respectively. The terminal t½ of candesartan was approximately doubled in patients with severe renal impairment. The AUC of candesartan in patients undergoing haemodialysis was similar to that in patients with severe renal impairment.
In two studies, both including patients with mild to moderate hepatic impairment, there was an increase in the mean AUC of candesartan of approximately 20% in one study and 80% in the other study (see section 4.2). There is no experience in patients with severe hepatic impairment.


There was no evidence of abnormal systemic or target organ toxicity at clinically relevant doses. In preclinical safety studies candesartan had effects on the kidneys and on red cell parameters at high doses in mice, rats, dogs and monkeys. Candesartan caused a reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit). Effects on the kidneys (such as interstitial nephritis, tubular distension, basophilic tubules; increased plasma concentrations of urea and creatinine) were induced by candesartan which could be secondary to the hypotensive effect leading to alterations of renal perfusion. Furthermore, candesartan induced hyperplasia/hypertrophy of the juxtaglomerular cells. These changes were considered to be caused by the pharmacological action of candesartan. For therapeutic doses of candesartan in humans, the hyperplasia/hypertrophy of the renal juxtaglomerular cells does not seem to have any relevance.
Foetotoxicity has been observed in late pregnancy (see section 4.6).
Data from in vitro and in vivo mutagenicity testing indicates that candesartan will not exert mutagenic or clastogenic activities under conditions of clinical use.
There was no evidence of carcinogenicity.


Carmellose calcium
Hydroxypropylcellulose
Iron oxide, CI 77491 (E172) (only 8 mg, 16 mg and 32 mg tablets)
Lactose monohydrate
Magnesium stearate
Maize starch
Macrogol


Not applicable


3 years

This medicinal product does not require any special temperature storage conditions.


PVC/PVDC blister packs of 7, 14, 15, 15x1 (single dose unit), 20, 28, 30, 30x1 (single dose unit), 50, 50x1 (single dose unit), 56, 98, 98x1 (single dose unit), 100 and 300 tablets.
HDPE bottles of 100 and 250 tablets
Not all pack sizes may be marketed.


No special requirements


SAUDI INTERNATIONAL TRADING COMPANY LTD (SITCO) P.O. Box 5132, Riyadh 11422

2015-06-01
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