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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 active substance in Carelio is metoprolol. Metoprolol belongs to the group of medicines
called beta-blockers and is used for the treatment of high blood pressure (hypertension), the
long term treatment of angina pectoris (tightness in the chest), chronic heart failure (chronic
cardiac insufficiency), heart rhythm disorders and cardiovascular disorders with palpitations,
as well as for the prevention of migraine.
Due to its special formulation, which allows controlled release of the active substance, the
effect of Carelio prolonged-release tablets usually lasts 24 hours.
Carelio may be taken only when prescribed by a doctor and with ongoing medical monitoring.


When must Carelio not be used?
Carelio must not be taken if you have a known hypersensitivity to the active substance
metoprolol, to any of the other ingredients or to any other medicines that belong to the group
called beta-blockers.
In addition, Carelio must not be taken:
‒ if you have problems with the passage of electrical impulses from the heart’s upper
chambers (atria) to the lower chambers (ventricles) (2nd- and 3rd
‒ if you have an irregular heartbeat which is often very slow and sometimes very
fast (except if you have a permanent pacemaker),
-degree AV block),
Carelio PIL_en Pg. 1
Acino Pharma AG 2 / 4
‒ if you have problems with the passage of electrical impulses between the sinus
node and upper chamber of the heart (atrium),
‒ if you are suffering from shock,
‒ if you have a weak heart together with fluid accumulation in the lungs, poor blood
circulation or low blood pressure,
‒ if your resting pulse rate before treatment is less than 50 beats per minute,
‒ if you have abnormally low blood pressure,
‒ if the circulation in your arms or legs is severely reduced,
‒ if you are prone to bronchial asthma or bronchial spasms.
When caution is needed while taking Carelio?
This medicine may affect your reactions, your ability to use tools and machinery and your
ability to drive.
If you are taking other medicines for breathing disorders at the same time, the dosages of the
various medicines must be readjusted by a doctor.
Caution is advised in case of diabetes mellitus, certain heart conditions, heart conduction
disorders, circulatory disorders, impaired liver function as well as in patients with a hormoneproducing
tumour (phaeochromocytoma).
Before surgery the anaesthetist should be informed that you are taking Carelio .
Some medications (including nose and eye drops) as well as alcohol may interfere with the
action of Carelio if taken at the same time.
Tell your doctor or pharmacist if you suffer from other illnesses, have any allergies or are
taking any other medicines (including those purchased without a prescription).
May Carelio be taken during pregnancy or breast feeding?
If you are pregnant or intend to become pregnant, or if you are breast feeding, consult your
doctor before taking Carelio .
Carelio , a beta-blocker, may harm the foetus or induce premature labour.


Carelio prolonged-release tablets are taken once daily with a glass of water. They can be
taken with or without meals. The Carelio prolonged-release tablets have a score line and can
be easily divided. However, they must not be crushed or chewed.
The doctor will prescribe the right dose for you based on regular tests/examinations. In
general, the following dosage guidelines apply:
High blood pressure (hypertension)
In cases of mild to moderate high blood pressure, take 1 prolonged-release tablet of Carelio
50, once daily in the morning. The dosage may be increased by the doctor to 1 prolongedrelease
tablet of Carelio 100 or Carelio 200. If necessary, your doctor may prescribe an
additional blood-pressure lowering medicine for you.
Adults
For children from 6 years of age, the dosage depends on body weight. Your doctor will
determine the correct dosage for your child and monitor it regularly.
Children and adolescents (6 to 16 years of age)
The use of Carelio by children below 6 years of age is not recommended.
Carelio PIL_en Pg. 2
Acino Pharma AG 3 / 4
Angina pectoris (tightness in the chest)
In cases of angina pectoris, take 1 prolonged-release tablet of Carelio 100 or Carelio 200 once
daily. If necessary, your doctor may increase the dose.
Chronic heart failure (chronic cardiac insufficiency)
In cases of chronic heart failure, the initial dose is Carelio 25 mg once daily for 2 weeks.
In cases of severe heart failure, the doctor may prescribe you a lower initial dose of 12.5 mg
once daily (half a Carelio 25 mg prolonged-release tablet). The dose can then be doubled
every two weeks up to 200 mg Carelio once daily.
Heart rhythm disorders
In cases of heart rhythm disorders, take 1 prolonged-release tablet of Carelio 100 or Carelio
200 once daily. If necessary, your doctor may increase the dose.
Cardiovascular disorders with palpitations
In cases of cardiovascular disorders, take 1 prolonged-release tablet of Carelio 100 once daily.
If necessary, your doctor may increase the dose.
Prevention of migraine
For the prevention of migraine, take 1 prolonged-release tablet of Carelio 100 or Carelio 200
once daily.
You must not stop taking Carelio suddenly. The doctor will decide how to reduce the dose
gradually.
Do not change the prescribed dosage yourself. If you think that the effect of the medicine is
too weak or too strong, talk to your doctor or pharmacist.


The following side effects may occur when taking Carelio :
Very common: tiredness. Common: dizziness, headache, nausea, abdominal pain, shortness of
breath, abnormally slow pulse, cold hands and feet, diarrhoea and constipation.
Uncommon: exhaustion, vomiting, pain around the heart, oedema (water retention in the
tissues), muscle cramps, drowsiness, sleeplessness, nightmares, impaired concentration,
depression, increased sweating, rash, asthma attacks and weight gain. Rare: palpitations,
irregular heartbeat, heart failure, nervousness, anxiety, visual disturbances, dry and irritated
eyes, inflammation of the lining of the nose, muscle weakness, dry mouth, hair loss, libido
disorders and erectile dysfunction.
Very rare: mood swings, impaired memory, confusion, hallucinations, ringing in the ears,
taste disturbances, sensitivity of the skin to light, worsening of psoriasis and joint pain.
If you notice any side effects not described here, you should tell your doctor or pharmacist.


Do not store above 25°C and keep out of the sight and reach of children.
This medicine may be used only up to the date marked with “EXP” on the pack. If you have
out-of-date medication, return it to the pharmacy for disposal.
Further information may be obtained from your doctor or pharmacist. These persons have the
detailed prescribing information at their disposal.


1 prolonged-release tablet of Carelio 25, 50, 100 and 200 contains 23.75 mg, 47.5 mg, 95 mg
and 190 mg respectively of metoprolol succinate, equivalent to 25 mg, 50 mg, 100 mg and
200 mg respectively of metoprolol tartrate.


Packs of 30, 50 and 100 prolonged-release tablets are available (Carelio 25, Carelio 50, Carelio 100, Carelio 200).

Acino Pharma AG, Liesberg (Switzerland)


March 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)

المادة الفع الة في كاريليو هي ميتوبرولول. ينتمي ميتوبرولول إلى مجموعة من الأدوية تسمى حاصرات بيتا وتستخدم لعلاج ارتفاع
ضغط الدمَّ، وعلاج الذبحة الصدرية طويل الأمد (ضيق في الصدر)، فشل القلب المزمن (قصور مزمن بوظائف القلب)،
اضطرابات النظم القلبي واضطرابات القلب والأوعية الدمَّوية المصحوب بخفقان، وكذلك لمنع الإصابة بالصداع النصفي.
نظرًا لتركيبته الخاصة، التي تسمح بالإفراز المُضبط للمادة الفعَّالة، يدوم تأثير كاريليو أقراصممتدة الإفراز عادة لمدة ۲٤ ساعة.
لا يمكن تناوُل كاريليو إلا عند وصفه من قبل الطبيب مع المراقبة الطبية المستمرة.

متى يجب تجنبُّ استخدام كاريليو؟
يجب عدم تناوُل كاريليو إذا كنت مصاباً بفرط الحساسية المعروف تجاه المادة الفعاّلة ميتوبرولول، أو تجاه أي من المكونات
الأخرى أو تجاه أية أدوية أخرى تنتمي إلى مجموعة الأدوية التي تسمى حاصرات بيتا.
بالإضافة إلى ذلك، يجب تجنُّب تناوُل كاريليو في الحالات التالية:
‒ إذا كان لديك مشاكل خاصة بمرور الإشارات الكهربائية من غرف القلب العليا (الأذينين) إلى الغرف السفلى (البطينين)
(الإحصار الأذيني البطيني من الدرجة الثانية والثالثة).
‒ إذا كنت تعاني من عدم انتظام ضربات القلب والذي غالبًا ما يكون بطيء جدًا وأحيانًا سريع جدًا (باستثناء في حالة إذا
كان لديك منظم دائم لضربات القلب).
‒ إذا كان لديك مشاكل خاصة بمرور الإشارات الكهربائية بين العقُد الجيبية والغرفة العليا للقلب (الأذينين).
‒ إذا كنت تعُاني من صدمة.
‒ إذا كنت مصابًا بضعف القلب مصحوب بتراكُم السائل في الرئتين، أو ضعف الدورة الدموية أو انخفاض ضغط الدم.
‒ إذا كان معدل النبض لديك أثناء الراحة قبل العلاج أقل من ٥۰ ضربة في الدقيقة.
‒ إذا كان لديك انخفاض غير طبيعي في ضغط الدَّم.
‒ إذا كنت مصاباً بقصور الدورة الدموية في ذراعيك أو ساقيك بشدة.
‒ إذا كنت معرضًا للإصابة بمرض الربو الشُّعبَي أو تقلصات الشعب الهوائية.
Carelio PIL_ar Pg. 1
متى يلزم توخي الحذر أثناء تناوُل كاريليو؟
قد يؤثر هذا الدواء على ردود أفعالك وفي قدرتك على استخدام الأدوات أو الآلات وقدرتك على القيادة.
إذا كنت تتناول أدوية أخرى لعلاج اضطرابات التنفس في نفس الوقت، فيجب تعديل جرعة الأدوية المختلفة من قبل الطبيب.
ينُصح بتوخي الحذر في حالة الإصابة بمرض السُّكَّرِيّ وبعض حالات القلب، واضطرابات التوصيل بالقلب، واضطرابات الدورة
الدموية، وقصور وظائف الكبد وكذلك في المرضى الذين يعانون من ورم مفرز للهرمونات (ورم القواتم).
قبل الخضوع للجراحة يجب إخبار طبيب التخدير بأنك تتناول كاريليو.
قد تتداخل بعض الأدوية (بما في ذلك قطرات الأنف والعين) وكذلك الكحوليات مع عمل كاريليو إذا تم تناوُلها في الوقت نفسه.
يرُجى إبلاغ طبيبك أو الصيدلي الخاص بك إذا كنت تعاني من أي أمراض أخرى أو أي حساسية، أو إذا كنت تتناول أية أدوية
أخرى (بما في ذلك الأدوية التي يتم شراؤها بدون وصفة طبية).
هل يجوز تناوُل كاريليو خلال فترة الحمل أو الرضاعة الطبيعية؟
استشيري طبيبك قبل تناوُل كاريليو إذا كنتِ حاملا أو تنوين الحمل، أو كنتِ مرض

https://localhost:44358/Dashboard

يتم تناوُل كاريليو أقراص ممتدة الإفراز مرة واحدة يومياً مع كوب من الماء. يمكن تناوُل الأقراص مع الوجبات أو بدونها. تكون
أقراص كاريليو ممتدة الإفراز بها خط تقسيم ومن الممكن تقسيمها بسهولة. مع ذلك، يجب عدم طحن الأقراص أو مضغها.
سيصف لك الطبيب الجرعة الصحيحة لك اعتماداً على الاختبارات/ الفحوصات المنتظمة. بصفة عامة، يتم تطبيق إرشادات
الجرعة التالية:
ارتفاع ضغط الدم
البالغون U
في حالة الإصابة بارتفاع ضغط الدمَّ البسيط إلى معتدل، تناول قرصًا واحد ممتد الإفراز من كاريليو ٥۰ ، مرة واحدة يوميًا في
الصباح. قد يقوم الطبيب بزيادة الجرعة إلى قرص واحد ممتد الإفراز من كاريليو ۱۰۰ أو كاريليو ۲۰۰ . إذا لزم الأمر، فقد يصف
لك طبيبك دواءً إضافيًا خافضًا لضغط الدم.
الأطفال والمراهقون (بعمر ٦ إلى ۱٦ عامًا) U
بالنسبة للأطفال من عمر ٦ سنوات، تعتمد الجرعة على وزن الجسم. سيحدد طبيبك الجرعة الصحيحة لطفلك ويراقبها بانتظام.
لا يوصى باستخدام كاريليو من قبل الأطفال الذين تقل أعمارهم عن ٦ سنوات.
الذبحة الصدرية (ضيق في الصدر)
في حالة الإصابة بالذبحة الصدرية، تناول قرصًا واحدًا ممتد الإفراز من كاريليو ۱۰۰ أو كاريليو ۲۰۰ مرَّة واحدة يومياً. إذا كانت
هناك حاجة، فقد يقوم طبيبك بزيادة الجرعة.
فشل القلب المزمن (قصور مزمن بوظائف القلب)
في حالات فشل القلب المزمن، تكون الجرعة الأوَّلية من كاريليو ۲٥ مجم مرة واحدة يوميًا لمدة ۲ أسابيع.
في حالات فشل القلب الشديد، قد يصف لك الطبيب جرعة أوَّلية منخفضة بحجم ۱۲٫٥ مجم مرَّة واحدة يوميًا (نصف قرص ممتد
الإفراز من كاريليو ۲٥ مجم). من الممكن حينئذ مضاعفة الجرعة كل أسبوعين حتى تصل إلى ۲۰۰ مجم من كاريليو مرَّة واحدة
يومياً.
اضطرابات النظم القلبي
في حالة الإصابة باضرابات النظم القلبي، تناول قرصًا واحدًا ممتد الإفراز من كاريليو ۱۰۰ أو كاريليو ۲۰۰ مرَّة واحدة يومياً.
إذا كانت هناك حاجة، فقد يقوم طبيبك بزيادة الجرعة.
اضطرابات القلب والأوعية الدمَّوية المصحوبة بخفقان
في حالة الإصابة باضرابات القلب والأوعية الدموية، تناول قرصًا واحداً ممتد الإفراز من كاريليو ۱۰۰ مرَّة واحدة يومياً. إذا
كانت هناك حاجة، فقد يقوم طبيبك بزيادة الجرعة.
الوقاية من الصداع النصفي
للوقاية من الصداع النصفي، تناول قرصًا واحدًا ممتد الإفراز من كاريليو ۱۰۰ أو كاريليو ۲۰۰ مرَّة واحدة يومياً.
ا. 􀌒 يجب عدم إيقاف كاريليو فجأة. سيقرر طبيبك كيفية خفض الجرعة تدريجي
لا تغير الجرعة الموصوفة من تلقاء نفسك. إذا شعرت أن تأثير الدواء أقل من اللازم أو أقوى من اللازم، فاتصل بطبيبك أو
بالصيدلي الخاص بك.

٤. الآثار الجانبية المُحتملة
قد تحدث الآثار الجانبية التاَّلية عند تناوُل كاريليو:
شائعة جدا: تعب. شائعة: دوخة، صداع، غثيان، ألم بالبطن، ضيق النفس، بطء النبض الغير طبيعي، برودة اليدين والقدمين،
الإسهال والإمساك.
غير شائعة: إنهاك، قيء، ألم حول القلب، وذمة (احتباس الماء في الأنسجة)، تقلصات عضلية، نعاس، عدم القدرة على النوم
(أرق)، كوابيس، ضعف التركيز، اكتئاب، زيادة التعرُّق، طفح جلدي، نوبات الربو، زيادة الوزن. نادرة: خَفَقان، عدم انتظام
ضربات القلب، فشل القلب، العصبية، القلق، اضطرابات بصرية، جفاف وتهيج العينين، التهاب بطانة الأنف، ضعف العضلات،
جفافُ الفَم، تساقط الشعر، اضطرابات الرغبة الجنسية واضطرابات بالانتصاب.
ا: تقلب الحالة المزاجية، ضعف الذاكرة، ارتباك/التباس، الهلاوس، طنين بالأذنين، اضطرابات التذوق، حساسية الجلد 􀌒 نادرة جد
تجاه الضوء، تفاقم الصدفية وألم بالمفاصل.
إذا لاحظت أية آثار جانبية غير مذكورة في هذه النشرة، فيجب عليك إخبار طبيبك أو الصيدلي الخاص بك.

لا تحفظ الدَّواء في درجة حرارة تتجاوز ۲٥ درجة مئوية واحفظه بعيداً عن رؤية ومُتناوَل الأطفال.
على العبوة. إذا كانت لديك أدوية منتهية «EXP» من الممكن استخدام هذا الدوَّاء حتى تاريخ انتهاء الصلاحية المحدد بكلمة
الصلاحية، فقم بإعادتها إلى الصيدلية للتخلص منها.
قد يتم الحصول على معلومات إضافية من طبيبك أو الصيدلي الخاص بك. هؤلاء الأشخاص لديهم المعلومات الوصفية المفصلة

يحتوي قرص واحد ممتد الإفراز من كاريليو ۲٥ ، و ٥۰ ، و ۱۰۰ و ۲۰۰ على ۲۳٫۷٥ مجم، و ٤۷٫٥ مجم، و ۹٥ مجم و ۱۹۰ مجم
على التوَّالي من سكسينات الميتوبرولول، ما يعادل ۲٥ مجم، و ٥۰ مجم، و ۱۰۰ مجم و ۲۰۰ مجم على التوَّالي من طرطرات
الميتوبرولول.

.( تتوفر عبوات تحتوي على و ۳۰ ، و ٥۰ و ۱۰۰ قرصًا ممتد الإفراز (كاريليو ۲٥ ، كاريليو ٥۰ ، كاريليو ۱۰۰ ، كاريليو ۲۰۰

أسينو فارما إيه جي، ليزبيرج (سويسرا)

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

CarelioTM 25/50/100/200 mg Retard Tablets

Active substance: Metoprolol succinate. Excipients: Excipients for coated tablets.

One prolonged-release tablet contains 23.75 mg, 47.5 mg, 95 mg or 190 mg of metoprolol succinate, equivalent to 25 mg, 50 mg, 100 mg or 200 mg of metoprolol tartrate respectively.

Hypertension;
Angina pectoris (long-term prophylaxis);
Treatment of NYHA class II and III chronic heart failure, in addition to the standard
treatment;
Cardiac arrhythmias, especially supraventricular tachyarrhythmias;
Functional cardiovascular disorders with palpitations;
Prophylaxis of migraine.


Carelio prolonged-release tablets are taken once daily with a glass of water. They can be
taken with or without meals. The Carelio prolonged-release tablets have a score line and can
be easily divided to allow dosage adjustment. They must not be chewed or crushed.
The following dosage guidelines apply:

ypertension
Patients with mild or moderate hypertension: M 50 once daily in the morning.
For patients not responding to the Carelio 50 dose, Carelio 100 or Carelio 200 can be
administered once daily. If necessary, a further antihypertensive can additionally be
prescribed.
Hypertensive patients receiving long-term antihypertensive treatment with 100–200 mg of
Carelio once daily have shown a reduced mortality rate including sudden cardiac death as
well as a diminished rate of stroke and coronary events (see “Properties/Effects”).
Angina pectoris
Carelio 100 or Carelio 200 once daily.
In severe cases, the dose, given once daily, may be further increased.
Chronic heart failure
The dosage of Carelio should be adjusted individually for patients with chronic heart failure
who receive the standard therapy.
Starting dose: one 25 mg tablet once daily for 2 weeks.
The recommended starting dose for patients with NYHA class III heart failure is 12.5 mg
(half a 25 mg tablet) once daily during the first week of treatment. Thereafter, the dose can be
doubled every two weeks of treatment up to a maximum dose of 200 mg once daily. During
long-term therapy a maximum dose of 200 mg once daily (or the highest dose tolerated by the
individual patient) is recommended.
After each increase in the dose the tolerability of the treatment must be reviewed carefully. In
the event of hypotension a reduction in the dose(s) of the concomitant medication(s) will be
necessary. Incipient hypotension at the start of therapy does not necessarily mean that longterm
therapy will not be tolerated. In this case, however, the patient must take a lower dose
until his/her condition is stable.
Heart rhythm disorders
Carelio 100 or Carelio 200 once daily.
If necessary, the dose, given once daily, may be further increased.
Functional cardiovascular disorders with palpitations
Carelio 100 once daily.
If necessary, the dose, given once daily, may be further increased.
Prophylaxis of migraine
Carelio 100 or Carelio 200 once daily.
The treatment should not be stopped abruptly but tapered off, especially in patients with
coronary heart disease or after long-term use (See “Warnings and precautions”).
Special dosage instructions
Renal insufficiency
An adjustment of the dose is not necessary in patients with renal impairment.
Hepatic impairment
Because of low binding of metoprolol to plasma proteins (5-10%), a dose adjustment is
usually not necessary in patients with mild hepatic impairment. However, in patients with
Sequence SPC Pg. 2
severe hepatic impairment (e.g. patients who have undergone shunt surgery) the dose should
be adjusted accordingly.
Elderly patients
An adjustment of the dose is not necessary in elderly patients.
Paediatric population
The recommended starting dose for hypertensive patients > 6 years old is 1.0 mg/kg
metoprolol, with a maximum of 50 mg/day. This dose is administered once daily and must be
approximated to the Carelio tablets dose strengths. In patients who are not responsive to
1.0 mg/kg, the dose can be increased to a maximum of 2.0 mg/kg. Doses higher than 200 mg
once daily have not been studied in children and adolescents.
Efficacy and safety of use in children < 6 years old have not been studied.


Known hypersensitivity to the active substance metoprolol, other beta-receptor blockers and related derivatives or to any of the excipients. Second- or third-degree atrioventricular block, congestive heart failure (pulmonary oedema, impaired blood flow or hypotension), concomitant continuous or intermittent inotropic treatment with beta-agonists, clinically manifest sinus bradycardia, sick sinus syndrome (except in patients with a permanent pacemaker), severe peripheral arterial circulatory disturbances, cardiogenic shock, hypotension, bradycardia (pulse rate < 50 beats/min), untreated phaeochromocytoma (see “Warnings and precautions”). In cases of suspected acute myocardial infarction, patients should not take Carelio when the heart rate is < 45 beats/min, the PQ interval is > 0.24 sec or systolic blood pressure is < 100 mmHg. Carelio must also not be taken in the presence of severe heart failure (NYHA class IV). A history of severe bronchial asthma or severe bronchospasm.

Patients being treated with beta-receptor blockers should not receive intravenous
administrations of verapamil-type calcium antagonists.
In general, patients being treated for hypertension with concomitant obstructive pulmonary
disease should not receive beta-receptor blockers. Because of its cardioselectivity, Carelio can
still be administered in cases where relevant other medicines such as diuretics are not
tolerated or are ineffective. In such circumstances, the lowest effective dose must be chosen
and the dosage of the beta-2 stimulant must be re-adjusted.
Carelio may lead to an increased plasma concentration in the presence of genetically induced
debrisoquine polymorphism in poor metabolisers.
Metoprolol influences insulin release and carbohydrate metabolism to a lesser extent than
non-selective beta-receptor blockers. Unlike non-selective beta-receptor blockers, metoprolol
only partially masks hypoglycaemic symptoms in diabetic patients. Caution is nevertheless
advised. Diabetic patients should be warned that beta-receptor blockers can attenuate
tachycardia associated with hypoglycaemia; other signs of hypoglycaemia such as lightheadedness
or sweating may not be significantly suppressed. Sweating may even be
increased.

Patients with pre-existing cardiac decompensation should be treated for this before and during
metoprolol therapy.
A moderate AV conduction abnormality may worsen (to the point of AV block).
Metoprolol may exacerbate peripheral arterial circulatory disorders, mainly due to its
antihypertensive effect.
If metoprolol is given to patients with known phaeochromocytoma, an alpha-receptor blocker
should be administered concomitantly (see “Contraindications”).
In the case of liver cirrhosis, the bioavailability of beta-receptor blockers may be enhanced,
leading to an increase in plasma concentrations.
Abrupt discontinuation of therapy is dangerous, particularly in high-risk patients, and must
therefore be avoided.
Beta-receptor blocker medication should not be discontinued during surgery. Before surgery
the anaesthetist should be informed that the patient is being treated with metoprolol.
Patients undergoing surgery that does not involve the heart should not receive initial acute
treatment with high doses of metoprolol as this has been shown to be associated with
bradycardia, hypotension and stroke (including with a fatal outcome) in patients with
cardiovascular risk factors.
Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of
angina pectoris and, in some cases, myocardial infarction have occurred. When discontinuing
chronically administered metoprolol succinate extended-release tablets, particularly in
patients with ischemic heart disease, the dosage should be gradually reduced over a period of
1 - 2 weeks and the patient should be carefully monitored. If angina markedly worsens or
acute coronary insufficiency develops, metoprolol succinate extended-release tablet
administration should be reinstated promptly, at least temporarily, and other measures
appropriate for the management of unstable angina should be taken. Warn patients against
interruption or discontinuation of therapy without the physician's advice. Because coronary
artery disease is common and may be unrecognized, it may be prudent not to discontinue
metoprolol succinate extended-release tablet therapy abruptly even in patients treated only for
hypertension.
If treatment with Carelio is to be stopped, the metoprolol dose must be reduced gradually, if
possible, over a minimum of 2 weeks. It is recommended that half the dose (a tablet with a
lower active substance content) be taken each time until the final step, when half a 25 mg
tablet should be taken. The final dose level of 12.5 mg should be taken for at least 4 days
before treatment is stopped. If any symptoms appear during this cessation phase, dose
reduction must be slower. Abrupt cessation of the treatment may exacerbate chronic heart
failure and increase the risk of myocardial infarction and sudden cardiac death.
Patients with ischaemic heart disease in particular should be closely monitored during this
phase. The risk of coronary events including sudden cardiac death may be increased in the
beta-receptor blocker cessation phase.
Patients taking beta-receptor blockers who experience anaphylactic shock tend to show a
more severe form.


Metoprolol enhances the effect of other antihypertensive medicinal products. Special caution
is advised when a beta-receptor blocker is used concomitantly with prazosin for the first time.
Sequence SPC Pg. 4
Patients concomitantly receiving sympatholytic medicinal products, other beta-receptor
blockers (including in the form of eye drops) or MAO inhibitors should be monitored.
Nitroglycerine may enhance the antihypertensive effect of beta-receptor blockers.
If concomitant therapy with clonidine is to be terminated, therapy with the beta-receptor
blocker must be ended several days prior to clonidine.
When administered concomitantly with calcium channel blockers (of the verapamil/diltiazem
type) and/or anti-arrhythmic agents, attention should be paid to the possible occurrence of a
negative inotropic and chronotropic effect. Patients being treated with beta-receptor blockers
should not receive calcium channel blockers of the verapamil type intravenously.
Beta-receptor blockers may enhance the negative inotropic and negative dromotropic effects
of anti-arrhythmic agents (of the quinidine type and amiodarone).
Inhalation anaesthetics enhance the cardiodepressant effect in the presence of beta-receptor
blockade. Digitalis glycosides in association with beta-receptor blockers may increase
atrioventricular conduction time and induce bradycardia.
Metoprolol is a substrate of the cytochrome P450 isoenzyme CYP2D6. Substances that act as
enzyme inducers and enzyme inhibitors may therefore alter plasma concentrations of
metoprolol.
Co-administration with substances that are metabolised by CYP2D6, such as anti-arrhythmic
agents (e.g. amiodarone, quinidine), anti-histamine agents (e.g. diphenhydramine),
H2 receptor antagonists (e.g. cimetidine), antidepressants (e.g. clomipramine, selective
serotonin reuptake inhibitors [SSRIs]), antipsychotics (e.g. haloperidol) and COX-2 inhibitors
(e.g. celecoxib) as well as ritonavir, may increase plasma metoprolol concentrations. This
may potentiate the hypotensive effect of Carelio.
This must be taken into consideration when titrating the Carelio dose and attention must be
paid to the possibility of adverse effects, e.g. bradycardia.
Rifampicin may reduce the plasma metoprolol level. This may attenuate the hypotensive
effect of Carelio.
Alcohol may increase the plasma metoprolol concentration.
Concomitant treatment with indomethacin and some other inhibitors of prostaglandin
synthesis may reduce the antihypertensive effect of metoprolol.
When co-administered with adrenaline or other sympathomimetic substances (e.g. as
contained in cough remedies, nasal drops and eye drops), cardioselective beta-receptor
blockers in therapeutic doses lead to less pronounced hypertensive reactions than nonselective
beta-receptor blockers.
Caution is advised when treating diabetic patients with beta-receptor blockers. The diabetic
treatment should be adjusted.
Metoprolol may reduce the clearance of other medicinal products (e.g. lidocaine).


Pregnancy
Metoprolol should not be taken during pregnancy unless absolutely necessary.
There are no controlled studies in pregnant women.
In general, beta-receptor blockers reduce placental perfusion. Human studies have shown
indications of impaired placental perfusion due to metoprolol. This was associated with
growth retardation, intrauterine foetal death, abortion and premature labour. It is therefore
Sequence SPC Pg. 5
recommended that appropriate foetomaternal monitoring be performed in pregnant women
treated with metoprolol. Beta-receptor blockers may induce bradycardia in the foetus,
neonates or infants when breast feeding.
Animal studies have shown no direct or indirect toxicity affecting pregnancy, embryonic
development, foetal health and/or post-natal development.
Due to the possible development of adverse reactions, e.g. bradycardia, hypotension and
hypoglycaemia, in the neonate, therapy with metoprolol should be discontinued 48–72 hours
before the estimated time of delivery. If this is not possible, newborns must be carefully
monitored by a physician for 48–72 hours after delivery.
Lactation
Metoprolol should not be taken while breastfeeding unless absolutely necessary. Metoprolol
is excreted in human milk. At the time of delivery, serum concentrations in mother and child
are comparable. In breast milk, metoprolol reaches approximately three-fold the serum
concentration measured in the mother. With daily oral dosing of 200 mg metoprolol,
approximately 225 micrograms are excreted per litre of milk. Although the amount of active
substance ingested with breast milk is unlikely to pose any risk to the child, infants should be
monitored for signs of beta-blockade.


Carelio may impair patients’ reaction time when driving vehicles or using machines, as
dizziness is common and fatigue very common.


The following adverse effects have been mainly observed in clinical trials and during daily
use of conventional metoprolol tablets (metoprolol tartrate).
Blood and lymphatic system disorders
Very rare: Thrombocytopenia.
Psychiatric disorders
Uncommon: Depression, reduced concentration, somnolence or insomnia, nightmares.
Rare: Nervousness, anxiety.
Very rare: Personality changes (e.g. mood swings), amnesia/impaired memory, confusion,
hallucinations.
Nervous system disorders
Very common: Fatigue.
Common: Dizziness, headache.
Uncommon: Paraesthesia, asthenia.
Rare: Muscle weakness.
Eye disorders
Rare: Visual disturbances, dry and irritated eyes, conjunctivitis, reduced lachrymal secretion.
Sequence SPC Pg. 6
Ear and labyrinth disorders
Very rare: Tinnitus
Cardiac disorders
In common with all anti-arrhythmic agents, the treatment of rhythm disorders with betareceptor
blockers may cause arrhythmogenic effects.
Common: Bradycardia, palpitations.
Uncommon: Transient deterioration of the symptoms of heart failure, cardiogenic shock in
patients with acute myocardial infarction, 1st degree AV block, oedema, precordial pain.
Rare: Cardiac conduction disorders, heart failure, cardiac arrhythmias, Raynaud’s syndrome.
Vascular disorders
Common: Orthostatic disorders (very rarely associated with syncope), cold hands and feet.
Very rare: Gangrene in patients with existing severe circulatory disturbances.
Respiratory, thoracic and mediastinal disorders
Common: Exertional dyspnoea.
Uncommon: Bronchospasm, even in patients with no known history of obstructive pulmonary
disease.
Rare: Rhinitis.
Gastrointestinal disorders
Common: Nausea, abdominal pain, diarrhoea or constipation.
Uncommon: Vomiting.
Rare: Dry mouth.
Very rare: Taste alterations.
Hepatobiliary disorders
Rare: Liver function test abnormalities.
Very rare: Hepatitis.
Skin and subcutaneous tissue disorders
Uncommon: Erythema, rash (in the form of urticaria and psoriasiform and dystrophic skin
changes), increased sweating.
Rare: Alopecia.
Very rare: Photosensitivity, exacerbation of psoriasis.
Musculoskeletal and connective tissue disorders
Very rare: Arthralgia.
Uncommon: Muscle cramps.
Reproductive system
Rare: Libido disorders and impotence.
Sequence SPC Pg. 7
General disorders
Uncommon: Weight gain.


Symptoms
Symptoms of overdose can include hypotension, heart failure, bradycardia/bradyarrhythmia,
cardiac conduction abnormalities, atrioventricular block, cardiogenic shock, cardiac arrest,
bronchospasm, disorders of consciousness (up to coma), nausea, vomiting and cyanosis.
Concomitant ingestion of alcohol, antihypertensives, quinidine or barbiturates potentiates the
signs and symptoms.
Measures
In the event of an overdose, the clinically necessary measures should be taken to stabilise and
monitor the patient’s vital signs.


ATC code: C07AB02
Carelio is a controlled-release formulation for once-daily oral administration.
The prolonged-release tablet contains the active substance metoprolol succinate in a large
number of pellets. Each pellet is coated with a polymeric membrane. After ingestion, the
tablet dissolves very rapidly and the pellets disperse in the gastrointestinal tract and release
metoprolol there continuously for 20 hours. The release rate is independent of physiological
factors such as pH or peristalsis.
Metoprolol, the active substance in Carelio, is a cardioselective beta-1-receptor blocker. It
acts on beta-1 receptors, which are mainly located in the heart, at lower doses than required to
influence beta-2 receptors, which are mainly located in the bronchi and peripheral vessels.
Metoprolol does not have a membrane-stabilising effect or a partial agonist effect (intrinsic
sympathomimetic activity = ISA).
Metoprolol decreases or inhibits the agonist effects of catecholamines which cause an
increase in heart rate, cardiac output, cardiac contractility and blood pressure.
Sequence SPC Pg. 8
At high endogenous adrenaline levels, metoprolol has less effect on the control of blood
pressure than non-selective beta-receptor blockers.
The Carelio formulation leads to a balanced plasma concentration profile and an even effect
(β1 blockade) over 24 hours, unlike conventional tablet formulations of beta-1 blockers,
including metoprolol tartrate. Marked plasma concentration peaks do not occur on Carelio,
which improves clinical beta-1 selectivity. Therefore, adverse effects due to high plasma
concentration peaks, such as bradycardia and tired legs, are reduced.
In general, patients being treated for hypertension with concomitant obstructive pulmonary
disease should not receive beta-receptor blockers. Metoprolol can be administered in
combination with a beta-2 agonist to patients with obstructive pulmonary disease in cases
where relevant other medicines such as diuretics are not tolerated or are ineffective. Within
the therapeutic dose range, metoprolol counteracts the bronchodilation caused by beta-2
agonists less strongly than a non-selective beta-receptor blocker (see “Warnings and
precautions”).
Metoprolol influences insulin release and carbohydrate metabolism to a lesser extent than
non-selective beta-receptor blockers. Metoprolol affects cardiovascular response to
hypoglycaemia less than non-specific beta-receptor blockers. Caution is nevertheless advised.
Sensitivity to insulin may decrease on long-term treatment with metoprolol.
Short-term studies show that metoprolol may cause a slight increase in triglyceride levels and
a decrease in free fatty acids in the blood. In some cases, a slight decrease in the HDL fraction
has been noted, albeit to a lesser extent than with non-selective beta-receptor blockers. A
long-term study over several years showed a significant decrease in the cholesterol level.
Metoprolol treatment may enhance quality of life. Improved quality of life has been observed
in patients following myocardial infarction. The treatment has also enhanced the quality of
life of patients with chronic heart failure.
Effect on hypertension
Metoprolol has an antihypertensive effect in standing as well as lying patients.
At the beginning of treatment, metoprolol initially causes an increase in peripheral vascular
resistance.
During long-term treatment, a decrease in total peripheral resistance can be obtained due to
the regression of hypertrophy in the peripheral arterial vessels.
Long-term antihypertensive treatment with metoprolol has also achieved a reduction in leftventricular
hypertrophy and at the same time improved ventricular function/filling.
A 4-week study performed in 144 children and adolescents (from 6 to 16 years old) with
essential hypertension showed that 1.0 and 2.0 mg/kg metoprolol can reduce placebocorrected
systolic blood pressure (4 to 6 mmHg). A greater decrease in diastolic blood
pressure (5 mmHg) was observed with the dose of 2.0 mg/kg versus placebo. No evident
differences were found as a function of age, Tanner stage or race.
It has been noted that metoprolol treatment reduces the risk of death from cardiovascular
disease in cases of mild to moderate hypertension, especially due to a lowering of the risk
factor of “sudden cardiovascular death”. At the same time, these patients have a lower risk of
non-fatal or fatal myocardial infarction or of stroke.
Sequence SPC Pg. 9
Effect on angina pectoris
In angina pectoris patients, metoprolol decreases the frequency, the length and the intensity of
angina attacks. Moreover, metoprolol increases physical exercise tolerance.
Effect on chronic heart failure
In NYHA class II and III heart failure patients with an ejection fraction of ≤40%, the use of
Carelio in addition to the standard treatment leads to an improvement in the survival rate and
a reduction in the number of hospitalisations normally required due to a worsening of heart
failure.
Carelio treatment has also allowed the following objectives to be achieved:
‒ improvement in functional NYHA class;
‒ improvement in quality of life.
Effect on cardiac rhythm
Metoprolol is used to regulate the heart rate in cases of supraventricular tachycardia, atrial
fibrillation and ventricular extrasystole.
Effect on functional cardiac disorders with palpitations
Carelio is suitable for the treatment of functional cardiac disorders with palpitations.
Its effect on myocardial infarction has also been studied. In cases of suspected or confirmed
myocardial infarction, metoprolol reduces mortality by reducing the risk of sudden cardiac
death. This effect may be based on a preventive action against ventricular fibrillation. This
inhibitory effect on ventricular fibrillation is probably based on a dual mechanism: on the one
hand, a vagal effect, which has a positive influence on the electrophysiological stability of the
heart, and, on the other hand, a sympathetically mediated anti-ischaemic effect, which
improves contractility and heart rate and stabilises blood pressure.
After early or late intervention, a reduction in mortality has been demonstrated in high-risk
patients with a history of cardiovascular disorders as well as in patients with diabetes mellitus
and/or congestive heart failure. Metoprolol administration has also been shown to decrease
the frequency of non-fatal reinfarctions.
Carelio can also be used as an additional treatment in cases of hyperthyroidism.


Absorption/Distribution
Metoprolol is almost completely absorbed after oral administration. Due to an extensive firstpass
effect, systemic bioavailability following a single oral dose is approximately 50%. The
bioavailability of the prolonged-release tablets (delayed active-substance release) is
approximately 20-30% lower than that of conventional tablets. This reduction has, however,
been shown not to be clinically significant because the “area under the effect curve” (AUEC)
in terms of heart rate is identical for both formulations.
Only a small fraction of metoprolol, approximately 5-10%, is bound to plasma proteins.
Each prolonged-release tablet consists of several hundred pellets containing metoprolol
succinate. Each pellet is surrounded by a polymeric membrane, which controls metoprolol
succinate release.
After ingestion, the prolonged-release tablet disintegrates rapidly and the pellets are released
in the gastrointestinal tract. Metoprolol is released continuously for 20 hours. The elimination
Sequence SPC Pg. 10
half-life of metoprolol is 3.5 hours (see “Metabolism / Elimination”). This is the reason why a
balanced plasma level is achieved over a dosing interval of 24 hours. Metoprolol succinate
release is independent of pH and peristalsis.
Metabolism
Metoprolol is metabolised by oxidation in the liver, mainly by CYP2D6. Three major
metabolites without a pharmacological effect can be identified.
Carelio may lead to an increased plasma concentration in the presence of genetically induced
debrisoquine polymorphism in poor metabolisers.
Elimination
As a rule, approximately 95% of an oral dose of metoprolol can be recovered in the urine.
Approximately 5% of the dose is excreted unchanged in the urine. In isolated cases, this
figure can rise to 30%. The plasma half-life of metoprolol amounts to an average of 3.5 hours
(extremes: 1 and 9 hours). Total clearance is about 1 L/min.
Kinetics in special patient groups
Elderly patients
The pharmacokinetics of metoprolol is unchanged in elderly patients compared with younger
patients.
Paediatric population
The pharmacokinetic profile of metoprolol in children and adolescents (6 to 16 years old) is
similar to that in adults. Oral clearance (CL/F) seems to increase linearly with body weight.
Renal insufficiency
The systemic bioavailability and the elimination of metoprolol are unchanged in patients with
impaired renal function. Elimination of the metabolites, however, is reduced. Significant
metabolite accumulation has been observed in patients with a glomerular filtration rate (GFR)
of about 5 mL/min. However, this does not lead to an increased beta-receptor blocking effect
of metoprolol.
Hepatic impairment
Increased plasma levels of unchanged metoprolol must be expected in liver cirrhosis due to
the reduced biotransformation rate.
In patients with severe liver cirrhosis and a portacaval shunt, the bioavailability of metoprolol
may be increased and total clearance decreased. Patients with a portacaval shunt have a total
elimination rate of approximately 0.3 L/min and the area under the plasma concentration/time
curve (AUC) values are approximately six times higher than in healthy subjects.


Mutagenic and tumorigenic potential
Metoprolol has not been subject to extensive mutagenicity testing; previous studies have
shown no indications of a mutagenic potential.
Results from carcinogenicity studies in rats and mice are available, from which no
tumorigenic potential can be inferred.
Reproductive toxicity
Sequence SPC Pg. 11
Studies on two animal species (rat, rabbit) have shown no indications of any teratogenic
properties for metoprolol.


Tablet core:
Sugar spheres, Macrogol 6000, Polyacrylate dispersion 30%, Talc, Povidone, Cellulose
microcrystalline, Magnesium stearate, Colloidal Silica anhydrous.
Tablet coating:
Hypromellose, Talc, macrogol 6000, Titanium dioxide (E171).


None known to date.


36 months

Do not store above 25°C.
Store out of the sight and reach of children.


Aluminium/Aluminium blister and/or HDPE bottles with PP twist-off caps.
Packs:
Carelio 25: 30, 50, 100.
Carelio 50: 30, 50, 100.
Carelio 100: 30, 50, 100.
Carelio 200: 30, 50, 100.
Not all pack sizes may be marketed.


NA


Acino Pharma AG, Liesberg (Switzerland)

October 2018
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