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| نشرة الممارس الصحي | نشرة معلومات المريض بالعربية | نشرة معلومات المريض بالانجليزية | صور الدواء | بيانات الدواء |
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LOWRAC contains the active substance Amlodipine which belongs to a group of medicines called calcium
antagonists.
LOWRAC is used to treat high blood pressure (hypertension) or a certain type of chest pain called angina, a rare
form of which is Prinzmetal’s or variant angina.
In patients with high blood pressure your medicine works by relaxing blood vessels, so that blood passes through
them more easily. In patients with angina LOWRAC works by improving blood supply to the heart muscle which
then receives more oxygen and as a result chest pain is prevented. Your medicine does not provide immediate relief
of chest pain from angina
Do not take LOWRAC:
□ If you are allergic (hypersensitive) to Amlodipine, or any of the other ingredients of your medicine listed in section
6, or to any other calcium antagonists. This may be itching, reddening of the skin or difficulty in breathing.
□ If you have severe low blood pressure (hypotension).
□ If you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock
(a condition where your heart is unable to supply enough blood to the body).
□ If you suffer from heart failure after a heart attack.
Take special care with LOWRAC:
You should inform your doctor if you have or have had any of the following conditions:
□ Recent heart attack
□ Heart failure
□ Severe increase in blood pressure (Hypertensive crisis)
□ Liver disease
□ You are elderly and your dose needs to be increased
Use in children and adolescents
LOWRAC has not been studied in children under the age of 6 years. LOWRAC should only be used for
hypertension in children and adolescents from 6 years to 17 years of age (see section 3).
Taking other medicines:
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including
medicines obtained without a prescription.
LOWRAC may affect or be affected by other medicines, such as:
□ Ketoconazole, itraconazole (anti-fungal medicines)
□ Ritonavir, indinavir, nelfinavir (so called protease inhibitors used to treat HIV)
□ Rifampicin, erythromycin, clarithromycin (antibiotics)
□ Hypericum perforatum (St. John’s Wort)
□ Verapamil, diltiazem (heart medicines)
□ Dantrolene (infusion for severe body temperature abnormalities)
□ Tacrolimus, sirolimus, temsirolimus, and everolimus (medicines used to alter the way your immune system works)
□ Simvastatin (a cholesterol lowering medicine)
□ Cyclosporin (an immunosuppressant)
LOWRAC may lower your blood pressure even more if you are already taking other medicines to treat your high
blood pressure.
Taking LOWRAC with food and drink:
Grapefruit juice and grapefruit should not be consumed by people who are taking LOWRAC. This is because
grapefruit and grapefruit juice can lead to an increase in the blood levels of the active ingredient Amlodipine, which
can cause an unpredictable increase in the blood pressure lowering effect of LOWRAC.
Pregnancy and breastfeeding:
Pregnancy:
The safety of Amlodipine in human pregnancy has not been established.
If you think you might be pregnant, or are planning to get pregnant, you must tell your doctor before you take
LOWRACBreastfeeding:
Amlodipine has been shown to pass into breast milk in small amounts. If you are breast-feeding or about to start
breast-feeding you must tell your doctor before taking LOWRAC.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines:
LOWRAC may affect your ability to drive or use machines. If the tablets make you feel sick, dizzy or tired, or give
you a headache, do not drive or use machines and contact your doctor immediately.
Always take your medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if
you are not sure.
The recommended initial dose is LOWRAC 5 mg once daily. The dose can be increased to LOWRAC 10 mg once
daily.
Your medicine can be used before or after food and drinks. You should take your medicine at the same time each
day with a drink of water. Do not take LOWRAC with grapefruit juice.
Use in children and adolescents
For children and adolescents (6-17 years old), the recommended usual starting dose is 2.5 mg a day. The
maximum recommended dose is 5 mg a day.
It is important to keep taking the tablets\capsules. Do not wait until your tablets\capsules are finished before seeing
your doctor.
If you take more LOWRAC than you should:
Taking too many tablets may cause your blood pressure to become low or even dangerously low. You may feel
dizzy, lightheaded, faint or weak. If blood pressure drop is severe enough shock can occur. Your skin could feel cool
and clammy and you could lose consciousness. Seek immediate medical attention if you take too many LOWRAC
tablets\capsules.
If you forget to take LOWRAC:
Do not worry. If you forget to take a tablet\capsule, leave out that dose completely. Take your next dose at the right
time. Do not take a double dose to make up for a forgotten dose.
If you stop taking LOWRAC:
Your doctor will advise you how long to take your medicine. Your condition may return if you stop using your
medicine before you are advised.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist
Like all medicines, LOWRAC can cause side effects, although not everybody gets them.
Visit your doctor immediately if you experience any of the following very rare, severe side effects after taking this
medicine:
□ Sudden wheeziness, chest pain, shortness of breath or difficulty in breathing
□ Swelling of eyelids, face or lips
□ Swelling of the tongue and throat which causes great difficulty breathing
□ Severe skin reactions including intense skin rash, hives, reddening of the skin over your whole body, severe
itching, blistering, peeling and swelling of the skin, inflammation of mucous membranes (Stevens Johnson
Syndrome, toxic epidermal necrolysis) or other allergic reactions
□ Heart attack, abnormal heart beat
□ Inflamed pancreas which may cause severe abdominal and back pain accompanied with feeling very unwell
The following very common side-effects have been reported. If any of these cause you problems or if they last for
more than one week, you should contact your doctor:
Very common: may affect more than 1 in 10 people
□ Oedema ( uid retention)
The following common side-e ects have been reported. If any of these cause you problems or if they last for more than one
week, you should contact your doctor:
Common: may affect up to 1 in 10 people
□ Headache, dizziness, sleepiness (especially at the beginning of treatment)
□ Palpitations (awareness of your heart beat), flushing
□ Abdominal pain, feeling sick (nausea)
□ Altered bowel habits, diarrhoea, constipation, indigestion
□ Tiredness, weakness
□ Visual disturbance, double vision □ Muscle cramps □ Ankle swelling
Other side-effects that have been reported include the following list. If any of these get serious, or if you notice any
side-effects not listed in this leaflet, please tell your doctor or pharmacist:
Uncommon: affects 1 to 10 users in 1,000
□ Mood changes, anxiety, depression, sleeplessness
□ Trembling, taste abnormalities, fainting
□ Numbness or tingling sensation in your limbs; loss of pain sensation
□ Ringing in the ears
□ Low blood pressure
□ Sneezing/running nose caused by inflammation of the lining of the nose (rhinitis)
□ CoughDry mouth, vomiting (being sick)
□ Hair loss, increased sweating, itchy skin, red patches on skin, skin discoloration
□ Disorder in passing urine, increased need to urinate at night, increased number of times of passing urine
□ Inability to obtain an erection, discomfort or enlargement of the breasts in men
□ Pain, feeling unwell □ Joint or muscle pain, back pain
□ Weight increase or decrease
Rare: may affect up to 1 in 1000 people
□ Confusion
Very rare: may affect up to 1 in 10000 people
□ Decreased numbers of white blood cells, decrease in blood platelets which may result in unusual bruising or easy
bleeding
□ Excess sugar in blood (hyperglycaemia)
□ A disorder of the nerves which can cause weakness, tingling or numbness
□ Swelling of the gums
□ Abdominal bloating (gastritis)
□ Abnormal liver function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice), liver enzyme increase
which may have an effect on some medical tests
□ Increased muscle tension
□ Inflammation of blood vessels, often with skin rash
□ Sensitivity to light
□ Disorders combining rigidity, tremor, and/or movement disorders
If any of the side effects gets 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.
□ LOWRAC 5: Do not store above 30°C, protected from light.
□ LOWRAC 10: Do not store above 30°C.
□ Do not use LOWRAC after the expiry date which is stated on the carton and on the blister, after (EXP).Date.
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 substance is Amlodipine.
□ Each Capsule contains Amlodipine 5 mg as Amlodipine Besylate.
□ Each Tablet contains Amlodipine 10 mg as Amlodipine Besylate.
The other ingredients are:
□ LOWRAC 5: maize starch, microcrystalline cellulose, colloidal anhydrous silica, magnesium stearate, purified
water, hard gelatin capsule (White/Yellow, size 3).
□ LOWRAC 10: microcrystalline cellulose, dibasic calcium phosphate, sodium starch glycolate type A, magnesium
stearate.
The Jordanian pharmaceutical manufacturing co.(P.L.C.|)
يحتوي لوراك على المادة الفعالة أملوديبين والتي تنتمي إلى مجموعة من الأدوية التي تدعى مضادات الكالسيوم.
يستخدم لوراك لعلاج ارتفاع ضغط الدم أو علاج نوع معين من آلام الصدرالتي تدعى الذبحة الصدرية ( ذبحة برنزميتال أو الذبحة الصدرية المخالفة
للمعتاد) وهي شكل نادر.
لدى المرضى الذين يعانون من ارتفاع ضغط الدم فإن هذا الدواء يعمل على إرخاء الأوعية الدموية، مما يسهل مرور الدم خلال هذه الأوعية. لدى
مرضى الذبحة الصدرية فإن لوراك يعمل على تحسين تدفق الدم إلى عضلة القلب وبالتالي تلقي المزيد من الأكسجين مما يؤدي إلى منع آلام لصدر.
هذا الدواء لا يؤدي إلى التخفيف الفوري لآلام الصدر الناتجة عن الذبحة الصدرية
لوراك
موانع استعمال لوراك:
إذا كنت تعاني من حساسية للأملوديبين أو لأي من مكونات الدواء المذكورة في قسم ٦ أو لأي من مضادات الكالسيوم. وقد تكون أعراضها حكة أو □
احمرار في الجلد أو صعوبة في التنفس.
إذا كنت تعاني من انخفاض شديد في ضغط الدم. □
إذا كنت تعاني من تضيق الصمام الأبهري في القلب أو من صدمة قلبية (حالة مرضية يكون فيها القلب غير قادر على تزويد الدم الكافي للجسم). □
إذا كنت تعاني من فشل في القلب بعد الإصابة بنوبة قلبية. □
الاحتياطات عند استعمال لوراك:
يجب إخبار طبيبك إذا كنت تعاني أو عانيت من أي من الحالات المرضية التالية:
نوبة قلبية حديثة □
فشل في القلب □
ارتفاع شديد في ضغط الدم □
أمراض الكبد □
إذا كنت كبير في السن وبحاجة إلى زيادة الجرعة □
الاستخدام لدى الأطفال والمراهقين
لم يتم دراسة الأملوديبين في الأطفال الذين تقل أعمارهم عن ٦ سنوات. يجب استخدام لوراك لعلاج ارتفاع ضغط الدم فقط في الأطفال والمراهقين
.( الذين تتراوح أعمارهم من ٦ سنوات إلى ۱۷ سنة (أنظر قسم ۳
التداخلات الدوائية من أخذ هذا المستحضر مع أي أدوية أخرى:
يرجى إخبار طبيبك أو الصيدلي إذا كنت تأخذ أو أخذت مؤخراً أي أدوية أخرى، بما في ذلك الأدوية التي تم الحصول عليها دون وصفة طبية.
قد يؤثر لوراك على الأدوية الأخرى أو قد يتأثر بها مثل:
كيتوكونازول، إيتراكونازول (أدوية مضادة للفطريات) □
ريتونافير، إندينافير، نيلفينافير (تسمى مثبطات البروتياز التي تستخدم لمعالجة فيروس نقص المناعة البشرية) □
ريفامبيسين، إيريثرومايسين، كلاريثرومايسين (مضادات حيوية) □
عشبة بيرفوراتوم (جونز ورت) □
فيراباميل، دايلتيازم (أدوية القلب) □
دانترولين (حقن لمعالجة ارتفاع درجة حرارة الجسم الشديدة وغير الطبيعية) □
تاكروليمس، سيروليمس، تيمسيروليمس، و إيفيروليمس (أدوية تستخدم لتغير طريقة عمل الجهاز المناعي) □
سيمفاستاتين (أدوية لخفض الكوليستيرول) □
سايكلوسبورين (مثبط للمناعة) □
قد يؤدي لوراك إلى خفض ضغط الدم لديك بشكل أكبر في حالة استخدام أدوية أخرى لعلاج ضغط الدم المرتفع.
تناول لوراك مع الطعام والشراب:
يجب عدم تناول الجريب فروت أو عصيره لدى الأشخاص الذين يتناولون لوراك. وذلك لأنه يؤدي إلى زيادة نسبة الأملوديبين المادة الفعالة في الدم
مما يسبب زيادة غير متوقعة لتأثير لوراك الخافض لضغط الدم.
الحمل والرضاعة:
الحمل:
لم تثبت سلامة الأملوديبين في الحمل لدى الإنسان.
يجب إخبار طبيبك قبل تناول لوراك إذا كنت تعتقدين بأنك حاملاً أو تفكرين بالإنجاب.
الرضاعة:
وقد تبين أن أملوديبين يمر في حليب الثدي بكميات صغيرة. يجب إخبار طبيبك قبل تناول لوراك إذا كنت مرضعة أو على وشك البدء بالإرضاعإسألي طبيبك أو الصيدلي للحصول على المشورة قبل تناول أي دواء.
تأثير المستحضر على القيادة واستخدام الآلات:
قد يؤثر لوراك على قدرتك على القيادة أو على استخدام الآلات. إذا سبب لك تناول الأقراص غثيان أو دوخة أو تعب أو صداع فإن عليك التوقف عن
القيادة أو استخدام الآلات واستشارة طبيبك مباشرةً
تناول لوراك تماماً كما أخبرك طبيبك. يجب التأكد من طبيبك أو الصيدلي إذا لم تكن متأكداً.
جرعة البدء التي ينصح هي لوراك ٥ ملغم مرة واحدة يومياً. يمكن زيادة الجرعة إلى ۱۰ ملغم مرة واحدة يومياً.
يمكن استخدام الدواء قبل أو بعد الطعام والشراب. يجب تناول الدواء في نفس الوقت كل يوم مع الماء. لا تتناول لوراك مع عصير الجريب فروت.
الاستخدام لدى الأطفال والمراهقين
۱۷ سنة) هي ۲٫٥ ملغم يومياً. الجرعة القصوى الموصى بها هي ٥ ملغم يومياً. - جرعة البدء الموصى بها للأطفال والمراهقين ( ٦
من المهم الحفاظ على تناول الأقراص/الكبسولات. لا تنتظر حتى تنتهي لديك الأقراص / الكبسولات قبل رؤية الطبيب.
الجرعة الزائدة من لوراك:
تناول العديد من الأقراص قد يؤدي إلى انخفاض ضغط الدم أو حتى انخفاضاً خطيراً. قد تشعر بدوخة، دوار، إغماء أو ضعف. إذا كان انخفاض
ضغط الدم شديد فإنه قد يؤدي إلى حدوث صدمة. قد تصبح بشرتك باردة و رطبة وقد تفقد الوعي. إذا تناولت العديد من الأقراص/الكبسولات فإن
عليك تلقي العناية الطبية الفورية.
نسيان تناول لوراك:
لا تقلق إذا كنت قد نسيت تناول القرص/الكبسولة، واترك هذه الجرعة تماماً. تناول الجرعة التالية في وقتها الصحيح. لا تتناول جرعة مضاعفة
لتعويض الجرعة المنسية.
التوقف عن تناول لوراك:
سيخبرك طبيبك عن المدة التي يجب أن تتناول الدواء فيها. قد تعود حالتك إلى وضعها السابق إذا توقفت عن تناول الدواء قبل الحصول على
النصيحة.
إذا كان لديك أي أسئلة أخرى حول استخدام هذا الدواء، اسأل طبيبك أو الصيدلي
كغيره من الأدوية، فقد يسبب لوراك أعراضاً جانبية، بالرغم من أنها لاتحدث للجميع.
قم بزيارة طبيبك على الفور إذا حدثت لك أي من الأعراض الجانبية التالية الشديدة والنادرة جداً بعد تناول هذا الدواء:
أزيز مفاجئ، ألم في الصدر، ضيق في التنفس أو صعوبة في التنفس □
تورم الجفون أو الوجه أو الشفاه □
تورم اللسان والحلق الذي يؤدي إلى صعوبة كبيرة في التنفس □
تفاعلات جلدية شديدة بما في ذلك طفح جلدي شديد، شرى، احمرار الجلد في الجسم كله، حكة شديدة، تقرحات، تقشر وتورم الجلد، التهاب الاغشية □
المخاطية (متلازمة ستيفينزجونسون، تَقَشُّرُ الأنسجة المُتَمَوِّتَةِ البَشْرَوِيَّةِ التسممي) أو غيرها من تفاعلات الحساسية
نوبة قلبية، ضربات قلب غير طبيعية □
التهاب البنكرياس الذي قد يسبب الآماً شديدة في البطن والظهر مصحوبة بتوعك شديد □
تم الإبلاغ عن الأعراض الجانبية الشائعة جداً التالية، فإذا أدت أي من هذه الأعراض إلى مشاكل أو إذا استمرت لأكثر من أسبوع، فإنه يجب عليك
استشارة طبيبك:
الأعراض الشائعة جداً: قد تؤثرعلى أكثر من شخص واحد في ۱۰ أشخاص
وذمة (احتباس السوائل) □
تم الإبلاغ عن الأعراض الجانبية الشائعة جداً التالية، فإذا أدت أي من هذه الأعراض إلى مشاكل أو إذا استمرت لأكثر من أسبوع، فإنه يجب عليك
استشارة طبيبك:
الأعراض الشائعة: قد تؤثرعلى شخص واحد في ۱۰ أشخاص
صداع، دوخة، نعاس (وخاصة في بداية المعالجة) □
خفقان (انتبه لنبضات قلبك) ،احمرار الوجه □
آلام في البطن، غثيان □
تغير حالة الأمعاء، إسهال، إمساك، عسر الهضم □
تعب، ضعف □
اضطرابات بصرية، الرؤية المزدوجة □
تشنجات العضلات □
تورم الكاحل □
تشمل الأعراض الجانبية الأخرى التي تم الإبلاغ عنها القائمة التالية، إذا أصبحت أي من هذه الأعراض خطيرة أو إذا لاحظت أي أعراض غير
مذكورة في هذه النشرة، يرجى إخبار طبيبك أو الصيدلي:
الأعراض غير الشائعة: قد تؤثرعلى شخص واحد في ۱۰۰ أشخاص
تغيرات المزاج، قلق، اكتئاب،أرق □
رجفة، تشوهات تذوق، إغماء، ضعف □
الشعور بالوخز أو الخدر في الأطراف، فقد الاحساس بالألم □
رنين في الأذن □
انخفاض ضغط الدم □
العطس/سيلان الأنف الناتج عن التهاب بطانة الأنف □
سعال □
جفاف الفم، تقيؤ □
فقدان الشعر، زيادة التعرق، حكة في الجلد، بقع حمراء على الجلد، تبدل لون الجلدعدم القدرة على الحصول على الانتصاب، عدم ارتياح أو تضخم الثدي عند الرجال □
ألم ، الشعور بتوعك □
ألم المفاصل أو العضلات، ألم الظهر □
زيادة أو نقصان الوزن □
الأعراض النادرة: قد تؤثرعلى شخص واحد في ۱۰۰۰ شخص
ارتباك □
الأعراض النادرة جداً: قد تؤثرعلى شخص واحد في ۱۰۰۰۰ شخص
انخفاض عدد خلايا الدم البيضاء، انخفاض الصفائح الدموية الذي يؤدي إلى كدمات غير عادية أو سهولة النزيف (تلف خلايا الدم الحمراء) □
فرط سكر الدم □
خلل الأعصاب الذي يؤدي إلى الضعف، الوخز أو الخدر □
تورم اللثة □
انتفاخ البطن □
وظائف الكبد غير الطبيعية، التهاب الكبد، اصفرار الجلد، زيادة إنزيمات الكبد التي قد يكون لها تأثيرعلى بعض الفحوصات الطبية □
زيادة التوتر العضلي □
التهاب الأوعية الدموية وغالباً مع طفح جلدي □
الحساسية للضوء □
اضطرابات التصلب، رعاش، و/أو اضطرابات الحركة □
إذا أصبحت أي من هذه الأعراض الجانبية خطيرة، أو إذا لاحظت أية أعراض جانبية غير المدرجة في
يحفظ بعيداً عن متناول الأطفال. □
لوراك ٥: لا يحفظ بدرجة حرارة أعلى من ۳۰ °م، محمي من الضوء. □
لوراك ۱۰ : لا يحفظ بدرجة حرارة أعلى من ۳۰ °م. □
لا ينبغي استعمال لوراك بعد تاريخ انتهاء الصلاحية الموجود على العلبة وعلى شريط الدواء. □
لا ينبغي التخلص من الأدوية من خلال مياه الصرف الصحي أو المنزلي. اسأل الصيدلاني عن كيفية التخلص من الأدوية التي لم تعد مطلوبة. سوف
تساعد هذه الاجراءات على حماية البيئة
المادة الفعالة هي أملوديبين.
كل كبسولة تحتوي على أملوديبين ٥ ملغم على هيئة أملوديبين بيسيليت. □
كل قرص يحتوي على أملوديبين ۱۰ ملغم على هيئة أملوديبين بيسيليت. □
المكونات الأخرى هي:
لوراك ٥: نشا الذرة، سليلوز بلوري مكروي، سيليكا غروية لامائية، ستيارات المغنيزيوم، مياه نقية، جيلاتين الكبسولة الصلب (أبيض/أصفر، □
.( حجم ۳
لوراك ۱۰ : سليلوز بلوري مكروي، فوسفات الكالسيوم ثنائي القاعدة، غليكولات نشا الصوديوم نوع أ، ستيارات المغنيزيوم.
وغطاء أصفر مطبوع عليه LOWRAC® كبسولات لوراك ٥ هي كبسولات جيلاتينية صلبة أسطوانية تتكون من جسم أبيض مطبوع عليه □ 5 مملوءة بمسحوق شبه أبيض إلى أبيض مصفر. mg على جهة واحدة . “AM أقراص لوراك ۱۰ هي أقراص بيضاء إلى سكرية اللون دائرية مسطحة مائلة الحافة منقوش عليها ” 10 □ علب تحتوي على ۱٤ كبسولة من لوراك ٥ محفوظة في أشرطة. □ علب تحتوي على ۲۸ كبسولة من لوراك ٥ محفوظة في أشرطة. □ علب تحتوي على ۳۰ قرص من لوراك ۱۰ محفوظة في أشرطة. □
الشركة الاردنية لانتاج الادوية المساهمة العامة
1-1 Therapeutic indications
q Hypertension
q Chronic stable angina pectoris
q Vasospastic (Prinzmetal's) angina.
Posology
Adults:
For both hypertension and angina the usual initial dose is 5 mg LOWRAC once daily which may be increased to a maximum dose of 10 mg depending on the individual patient's response.
In hypertensive patients, LOWRAC has been used in combination with a thiazide diuretic, alpha blocker, beta blocker, or an angiotensin converting enzyme inhibitor. For angina, LOWRAC may be used as monotherapy or in combination with other antianginal medicinal products in patients with angina that is refractory to nitrates and/or to adequate doses of beta blockers.
No dose adjustment of LOWRAC is required upon concomitant administration of thiazide diuretics, beta blockers, and angiotensin-converting enzyme inhibitors.
Special populations
Elderly patients:
LOWRAC used at similar doses in elderly or younger patients is equally well tolerated. Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care (see sections 4.4 and 5.2).
Patients with hepatic impairment:
Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautious and should start at the lower end of the dosing range (see sections 4.4 and 5.2). The pharmacokinetics of Amlodipine have not been studied in severe hepatic impairment. Amlodipine should be initiated at the lowest dose and titrated slowly in patients with severe hepatic impairment.
Patients with renal impairment:
Changes in Amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.
Paediatric population:
Children and adolescents with hypertension from 6 years to 17 years of age.
The recommended antihypertensive oral dose in paediatric patients ages 6-17 years is 2.5 mg once daily as a starting dose, up-titrated to 5 mg once daily if blood pressure goal is not achieved after 4 weeks. Doses in excess of 5 mg daily have not been studied in paediatric patients (see sections 5.1 and 5.2).
Children under 6 years old:
No data are available.
Method of administration
Capsule for oral administration
The safety and efficacy of Amlodipine in hypertensive crisis has not been established.
Patients with Cardiac failure
Patients with heart failure should be treated with caution. In a long-term, placebo controlled study in patients with severe heart failure (NYHA class III and IV) the reported incidence of pulmonary oedema was higher in the Amlodipine treated group than in the placebo group. Calcium channel blockers, including Amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.
Patients with hepatic impaired
The half life of Amlodipine is prolonged and AUC values are higher in patients with impaired liver function; dosage recommendations have not been established. Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Slow dose titration and careful monitoring may be required in patients with severe hepatic impairment.
Elderly patients
In the elderly increase of the dosage should take place with care (see sections 4.2 and 5.2).
Patients with renal impaired
Amlodipine may be used in such patients at normal doses. Changes in Amlodipine plasma concentrations are not correlated with degree of renal impairment. Amlodipine is not dialysable.
Effects of other medicinal products on Amlodipine
q CYP3A4 inhibitors: Concomitant use of Amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in Amlodipine exposure. The clinical translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose adjustment may thus be required.
q CYP3A4 inducers: upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine may vary. Therefore, blood pressure should be moniterd and dose regulation considered both during and after concomitant medication particulary with strong CYP3A4 inducers (e.g. rifampicin, hypericum perforatum.
q Administration of Amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.
q Dantrolene (infusion): In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalemia, it is recommended that the co-administration of calcium channel blockers such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.
Effects of Amlodipine on other medicinal products
q The blood pressure lowering effects of Amlodipine adds to the blood pressure-lowering effects of other medicinal products with antihypertensive properties.
q Tacrolimus: There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the pharmacokinetic mechanism of this interaction is not fully understood. In order to avoid toxicity of tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.
q Mechanistic Target to Rapamycin (mTOR) Inhibitors: mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of mTOR inhibitors.
q Cyclosporine: No drug interaction studies have been conducted with cyclosporine and amlodipine in healthy volunteers or other populations with the exception of renal transplant patients, where variable trough concentration increases (average 0% - 40%) of cyclosporine were observed. Consideration should be given for monitoring cyclosporine levels in renal transplant patients on amlodipine, and cyclosporine dose reductions should be made as necessary.
q Simvastatin: Co-administration of multiple doses of 10 mg of Amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin to 20 mg daily in patients on Amlodipine.
q In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin or warfarin.
Pregnancy
The safety of Amlodipine in human pregnancy has not been established.
In animal studies, reproductive toxicity was observed at high doses (see section 5.3).
Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus.
Breast-feeding
Amlodipine is excreted in human milk. The proportion of the maternal
dose received by the infant has been estimated with an interquartile
range of 3–7%, with a maximum of 15%.
The effect of amlodipine on infants is unknown. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with amlodipine should be made taking into account the benefit of breast-feeding to the child and the benefit of amlodipine therapy to the mother.
Fertility
Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of Amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3).
Amlodipine can have minor or moderate influence on the ability to drive and use machines. If patients taking Amlodipine suffer from dizziness, headache, fatigue or nausea the ability to react may be impaired. Caution is recommended especially at the start of treatment
Summary of the safety profile
The most commonly reported adverse reactions during treatment are somnolence, dizziness, headache, palpitations, flushing, abdominal pain, nausea, ankle swelling, oedema and fatigue.
Tabulated list of adverse reactions
The following adverse reactions have been observed and reported during treatment with Amlodipine with the following frequencies: 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); very rare (≤1/10,000).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
System Organ Class |
Frequency
|
Adverse reactions
|
Blood and lymphatic system disorders | Very rare | Leukocytopenia, thrombocytopenia |
Immune system disorders | Very rare | Allergic reactions
|
Metabolism and nutrition disorders | Very rare | Hyperglycaemia |
Psychiatric disorders | Uncommon | Insomnia, mood changes (including anxiety), depression |
Rare | Confusion | |
Nervous system disorders | Common | Somnolence, dizziness, headache (especially at the beginning of the treatment) |
Uncommon | Tremor, dysgeusia, syncope, hypoesthesia, paresthesia | |
Very rare | Hypertonia, peripheral neuropathy | |
Eye disorders | common | Visual disturbance (including diplopia) |
Ear and labyrinth disorders | Uncommon | Tinnitus |
Cardiac disorders | Common | Palpitations |
Uncommon | Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) | |
Very rare | Myocardial infarction | |
Vascular disorders | Common | Flushing |
Uncommon | Hypotension | |
Very rare | Vasculitis | |
Respiratory, thoracic and mediastinal disorders | common | Dyspnoea |
Uncommon | Cough, rhinitis | |
Gastrointestinal disorders | Common | Abdominal pain, nausea , dyspepsia, altered bowel habits (including diarrhoea and constipation), |
Uncommon | Vomiting, dry mouth | |
Very rare | Pancreatitis, gastritis, gingival hyperplasia | |
Hepatobiliary disorders | Very rare | Hepatitis, jaundice, hepatic enzymes increased* |
Skin and subcutaneous tissue disorders | Uncommon | Alopecia, purpura, skin discolouration, hyperhidrosis, pruritus, rash, exanthema, urticaria |
Very rare | Angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, Quincke oedema, photosensitivity | |
Not known | Toxic epidermal necrolysis | |
Musculoskeletal and connective tissue disorders | Common | Ankle swelling, muscle cramps |
Uncommon | Arthralgia, myalgia, back pain | |
Renal and urinary disorders | Uncommon | Micturition disorder, nocturia, increased urinary frequency |
Reproductive system and breast disorders | Uncommon | Impotence, gynaecomastia |
General disorders and administration site conditions | Very Common | Oedema |
common | asthenia, fatigue | |
Uncommon | Chest pain, pain, malaise | |
Investigations | Uncommon | Weight increase, weight decrease |
*mostly consistent with cholestasis
Exceptional cases of extrapyramidal syndrome have been reported.
To report any side effect (s):
Saudi Arabia: National Pharmacovigilance & Drug Safety Centre (NPC)
q Fax: +966-11-205-7662
q Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
q Toll free phone: 8002490000
q E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
In humans experience with intentional overdose is limited
Symptoms
Available data suggest that gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.
Treatment
Clinically significant hypotension due to Amlodipine overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output.
A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade.
Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours after administration of Amlodipine 10 mg has been shown to reduce the absorption rate of Amlodipine.
Since Amlodipine is highly protein-bound, dialysis is not likely to be of benefit.
Pharmacotherapeutic group: Calcium channel blockers, selective calcium channel blockers with mainly vascular effects.
ATC Code: C08CA01
Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle.
The mechanism of the antihypertensive action of Amlodipine is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which Amlodipine relieves angina has not been fully determined but Amlodipine reduces total ischaemic burden by the following two actions:
1) Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral resistance (afterload) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.
2) The mechanism of action of Amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischaemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (Prinzmetal's or variant angina).
In patients with hypertension, once daily dosing provides clinically significant reductions of blood pressure in both the supine and standing positions throughout the 24 hour interval. Due to the slow onset of action, acute hypotension is not a feature of Amlodipine administration.
In patients with angina, once daily administration of Amlodipine increases total exercise time, time to angina onset, and time to 1 mm ST segment depression, and decreases both angina attack frequency and glyceryl trinitrate tablet consumption.
Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and is suitable for use in patients with asthma, diabetes, and gout.
Use in patients with coronary artery disease (CAD)
The effectiveness of Amlodipine in preventing clinical events in patients with coronary artery disease (CAD) has been evaluated in an independent, multi-centre, randomized, double- blind, placebo-controlled study of 1997 patients; Comparison of Amlodipine vs. Enalapril to Limit Occurrences of Thrombosis (CAMELOT). Of these patients, 663 were treated with Amlodipine 5-10 mg, 673 patients were treated with enalapril 10-20 mg, and 655 patients were treated with placebo, in addition to standard care of statins, beta-blockers, diuretics and aspirin, for 2 years. The key efficacy results are presented in Table 1. The results indicate that Amlodipine treatment was associated with fewer hospitalizations for angina and revascularization procedures in patients with CAD.
Table 1. Incidence of significant clinical outcomes for CAMELOT | |||||||
| Cardiovascular event rates, No. (%) | Amlopidine vs. Placebo | |||||
Outcomes | Amlopidine | Placebo | Enalapril | Hazard Ratio (95% CI) | P Value | ||
Primary Endpoint |
|
|
|
| |||
Adverse cardiovascular events | 110 (16.6) | 151 (23.1) | 136 (20.2) | 0.69 (0.54-0.88) | .003 | ||
Individual Components |
|
|
|
|
| ||
Coronary revascularization | 78 (11.8) | 103 (15.7) | 95 (14.1) | 0.73 (0.54-0.98) | .03 | ||
Hospitalization for angina | 51 (7.7) | 84 (12.8) | 86 (12.8) | 0.58 (0.41-0.82) | .002 | ||
Nonfatal MI | 14 (2.1) | 19 (2.9) | 11 (1.6) | 0.73 (0.37-1.46) | .37 | ||
Stroke or TIA | 6 (0.9) | 12 (1.8) | 8 (1.2) | 0.50 (0.19-1.32) | .15
| ||
Cardiovascular death | 5 (0.8) | 2 (0.3) | 5 (0.7) | 2.46 (0.48-12.7) | .27 | ||
Hospitalization for CHF | 3 (0.5) | 5 (0.8) | 4 (0.6) | 0.59 (0.14-2.47) | .46 | ||
Resuscitated cardiac arrest | 0 | 4 (0.6) | 1 (0.1) | NA | .04 | ||
New-onset peripheral vascular disease | 5 (0.8) | 2 (0.3) | 8 (1.2) | 2.6 (0.50-13.4) | .24 | ||
Abbreviations: CHF, congestive heart failure; CI, confidence interval; MI, myocardial infarction; TIA, transient ischemic attack. | |||||||
Use in Patients with Heart Failure
Haemodynamic studies and exercise based controlled clinical trials in NYHA Class II-IV heart failure patients have shown that Amlodipine did not lead to clinical deterioration as measured by exercise tolerance, left ventricular ejection fraction and clinical symptomatology.
A placebo controlled study (PRAISE) designed to evaluate patients in NYHA Class III-IV heart failure receiving digoxin, diuretics and ACE inhibitors has shown that Amlodipine did not lead to an increase in risk of mortality or combined mortality and morbidity with heart failure.
In a follow-up, long term, placebo controlled study (PRAISE-2) of Amlodipine in patients with NYHA III and IV heart failure without clinical symptoms or objective findings suggestive or underlying ischaemic disease, on stable doses of ACE inhibitors, digitalis, and diuretics, Amlodipine had no effect on total cardiovascular mortality. In this same population Amlodipine was associated with increased reports of pulmonary oedema.
Treatment to prevent heart attack trial (ALLHAT)
A randomized double-blind morbidity-mortality study called the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was performed to compare newer drug therapies: Amlodipine 2.5-10 mg/d (calcium channel blocker) or lisinopril 10-40 mg/d (ACE-inhibitor) as first-line therapies to that of the thiazide-diuretic, chlorthalidone 12.5-25 mg/d in mild to moderate hypertension.
A total of 33,357 hypertensive patients aged 55 or older were randomized and followed for a mean of 4.9 years. The patients had at least one additional CHD risk factor, including: previous myocardial infarction or stroke (> 6 months prior to enrollment) or documentation of other atherosclerotic CVD (overall 51.5%), type 2 diabetes (36.1%), HDL-C < 35 mg/dL (11.6%), left ventricular hypertrophy diagnosed by electrocardiogram or echocardiography (20.9%), current cigarette smoking (21.9%).
The primary endpoint was a composite of fatal CHD or non-fatal myocardial infarction. There was no significant difference in the primary endpoint between amlodipine-based therapy and chlorthalidone-based therapy: RR 0.98 95% CI (0.90-1.07) p=0.65. Among secondary endpoints, the incidence of heart failure (component of a composite combined cardiovascular endpoint) was significantly higher in the Amlodipine group as compared to the chlorthalidone group (10.2% % vs 7.7%, RR 1.38, 95% CI [1.25-1.52] p<0.001). However, there was no significant difference in all-cause mortality between Amlodipine-based therapy and chlorthalidone-based therapy. RR 0.96 95% CI [0.89-1.02] p=0.20.
Use in children (aged 6 years and older)
In a study involving 268 children aged 6-17 years with predominantly secondary hypertension, comparison of a 2.5 mg dose, and 5.0 mg dose of Amlodipine with placebo, showed that both doses reduced Systolic Blood Pressure significantly more than placebo. The difference between the two doses was not statistically significant.
The long-term effects of amlodipine on growth, puberty and general development have not been studied. The long-term efficacy of Amlodipine on therapy in childhood to reduce cardiovascular morbidity and mortality in adulthood have also not been established.
Absorption, distribution, plasma protein binding: After oral administration of therapeutic doses, Amlodipine is well absorbed with peak blood levels between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80%. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.
The bioavailability of Amlodipine is not affected by food intake.
Biotransformation/elimination
The terminal plasma elimination half life is about 35-50 hours and is consistent with once daily dosing. Amlodipine is extensively metabolised by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.
Hepatic impairment
Very limited clinical data are available regarding Amlodipine administration in patients with hepatic impairment. Patients with hepatic insufficiency have decreased clearance of Amlodipine resulting in a longer half-life and an increase in AUC of approximately 40-60%.
Elderly population
The time to reach peak plasma concentrations of Amlodipine is similar in elderly and younger subjects. Amlodipine clearance tends to be decreased with resulting increases in AUC and elimination half-life in elderly patients. Increases in AUC and elimination half-life in patients with congestive heart failure were as expected for the patient age group studied.
Paediatric population
A population PK study has been conducted in 74 hypertensive children aged from 1 to 17 years (with 34 patients aged 6 to 12 years and 28 patients aged 13 to 17 years) receiving Amlodipine between 1.25 and 20 mg given either once or twice daily. In children 6 to 12 years and in adolescents 13-17 years of age the typical oral clearance (CL/F) was 22.5 and 27.4 L/hr respectively in males and 16.4 and 21.3 L/hr respectively in females. Large variability in exposure between individuals was observed. Data reported in children below 6 years is limited
Reproductive toxicology
Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of labour and decreased pup survival at dosages approximately 50 times greater than the maximum recommended dosage for humans based on mg/kg.
Impairment of fertility
There was no effect on the fertility of rats treated with Amlodipine (males for 64 days and females 14 days prior to mating) at doses up to 10 mg/kg/day (8 times* the maximum recommended human dose of 10 mg on a mg/m2 basis). In another rat study in which male rats were treated with Amlodipine besilate for 30 days at a dose comparable with the human dose based on mg/kg, decreased plasma follicle-stimulating hormone and testosterone were found as well as decreases in sperm density and in the number of mature spermatids and Sertoli cells.
Carcinogenesis, mutagenesis
Rats and mice treated with Amlodipine in the diet for two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. The highest dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 10 mg on a mg/m2 basis) was close to the maximum tolerated dose for mice but not for rats.
Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels.
*Based on patient weight of 50 kg.
1-1 List of excipients
q Maize starch
q Microcrystalline cellulose (Avicel pH 101)
q Colloidal anhydrous silica (Explotab)
q Magnesium stearate
q Purified water (Disappears after drying)
q Hard gelatin capsule (White/Yellow, size 3).
Not applicable.
Do not store above 30˚C, protect from light
q LOWRAC 5 Capsules are packed in boxes of 14 Capsules blistered in PVC/aluminium foil.
LOWRAC 5 Capsules are packed in boxes of 28 Capsules blistered in PVC/aluminium foil
No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements
