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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)

Vidonorm is prescribed for the treatment of high blood pressure (hypertension) and/or the treatment of stable coronary artery disease (a condition where the blood supply to the heart is reduced or blocked).

Patients already taking perindopril and amlodipine from separate tablets may instead receive one tablet of Vidonorm which contains both ingredients.

Vidonorm is a combination of two active ingredients, perindopril and amlodipine. Perindopril is an ACE (angiotensin converting enzyme) inhibitor. Amlodipine is a calcium antagonist (which belongs to a class of medicines called dihydropyridines). Together they work to widen and relax the blood vessels so that blood passes through them more easily and makes it easier for your heart to maintain a good blood flow.

 


1.      Do not take Vidonorm

-              if you are allergic to perindopril or any other ACE inhibitor, or to amlodipine or any other calcium antagonists, or any of the other ingredients of this medicine (listed in section 6). This may be itching, reddening of the skin or difficulty inbreathing.

-              if you are more than 3 months pregnant. (It is also better to avoid taking Vidonorm in early pregnancy - see section “Pregnancy”),

-              if you have experienced symptoms such as wheezing, swelling of the face or tongue, intense itching or severe skin rashes with previous ACE inhibitor treatment or if you or a member of your family have had these symptoms in any other circumstances (a condition called angioedema),

-              if you have cardiogenic shock (when the heart is unable to supply sufficient blood to the body), high grade aortic stenosis (narrowing of the main blood vessel leading from the heart),

-              if you have severe hypotension (very low bloodpressure),

-              if you have heart failure after acute myocardialinfarction,

-              if you have diabetes or impaired kidney function and you are treated with a blood pressure lowering medicine containing aliskiren.

 

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Vidonorm

-              if you have hypertrophic cardiomyopathy (heart muscle disease) or renal artery stenosis (narrowing of the artery which supplies the kidney withblood),

-              if you have any other heart problems,

-              if you have severe increase in blood pressure (Hypertensive crisis),

-              if you have liver problems,

-              if you have kidney problems or if you are receivingdialysis,

-              if you have collagen vascular disease (disease of the connective tissue) such as systemic lupus erythematosus or scleroderma,

-              if you have diabetes,

-             if you are on a salt restricted diet or use salt substitutes which contain potassium (a well balanced potassium blood level is essential),

-             if you are of black origin as ACE inhibitors may be less effective, but you may also more readily get angioedema,

-             if you are elderly,

-              if you are breast-feeding,

-              if you are taking any of the following medicines used to treat high blood pressure:

-              an “angiotensin II receptor blocker” (ARBs) (also known as sartans - for example valsartan, telmisartan, irbesartan), in particular if you have diabetes-related kidney problems,

-              aliskiren.

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. potassium) in your blood at regular intervals.

-              if you are taking any of the following medicines, the risk of angioedema is increased:

-              racecadotril (used to treat diarrhoea),

-              sirolimus, everolimus, temsirolimus and other drugs belonging to the class of so-called mTor inhibitors (used to avoid rejection of transplantedorgans).

You must tell your doctor if you think you are (or might become) pregnant. Vidonorm is not recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at that stage (see section “Pregnancy”).

See also information under the heading “Do not take Vidonorm

When you are taking Vidonorm, you should also inform your doctor or the medical staff if you:

-              are going to have a general anaesthetic and/or majorsurgery,

-              have recently suffered from diarrhoea or vomiting (beingsick),

-              are to undergo LDL apheresis (the removal of cholesterol from your blood by a machine),

-              are going to have desensitisation treatment to reduce the effects of an allergy to bee or wasp stings.

Children and adolescents

Vidonorm is not recommended for use in children and   adolescents.

Other medicines and Vidonorm

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Your doctor may need to change your dose and/or to take other precautions:

If you are taking other medicines for high blood pressure, including an angiotensin II receptor blocker (ARB) or aliskiren (see also information under the headings “Do not take Vidonorm” and “Warnings

and precautions”) or diuretics (medicines which increase the amount of urine produced by the kidneys).

 

You should avoid taking Vidonorm with:

-              lithium (used to treat mania or depression),

-              estramustine (used in cancer therapy),

-              potassium-sparing diuretics (spironolactone, triamterene), potassium supplements or potassium- containing salt substitutes.

 

Treatment with Vidonorm can be affected by other medicines. Your doctor may need to change your dose and/or to take other precautions.

Make sure to tell your doctor if you are taking any of the following medicines as special care may be required:

-              beta-blockers used in heart failure (bisoprolol, carvedilol, metoprolol),

-              non-steroidal anti-inflammatory drugs (e.g. ibuprofen) for pain relief or high dose aspirin,

-              medicines to treat diabetes (such as insulin or metformine),

-              medicines to treat mental disorders such as depression, anxiety, schizophrenia, etc. (e.g. tricyclic antidepressants, antipsychotics, imipramine-like antidepressants, neuroleptics),

-              allopurinol (for the treatment of gout),

-              procainamide (for the treatment of an irregular heartbeat),

-              vasodilators (like verapamil or diltiazem) including nitrates (products that widen the blood vessels),

-              heparin (medicines used to thin blood),

-              ephedrine, noradrenaline or adrenaline (medicines used to treat low blood pressure, shock or asthma),

-              baclofen or dantrolene (infusion), both used to treat muscle stiffness in diseases such as multiple sclerosis; dantrolene is also used to treat malignant hyperthermia during anaesthesia (symptoms including very high fever and muscle stiffness),

-              medicines used to treat bacterial (rifampicin, erythromycin or clarithromycin), HIV (ritonavir, indinavir, nelfinavir) or fungal infections (ketoconazole, itraconazole),

-              antiepileptic agents such as carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone,

-              alpha-blockers used for the treatment of enlarged prostate such as prazosin, alfuzosin, doxazosin, tamsulosin, terazosin,

-              amifostine (used to prevent or reduce side effects caused by other medicines or radiation therapy that are used to treat cancer),

-              corticosteroids (used to treat various conditions including severe asthma and rheumatoid arthritis),

-              the herbal remedy commonly known as St John's Wort (Hypericumperforatum),

-              gold salts, especially with intravenous administration (used to treat symptoms of rheumatoid arthritis).

-              immunosuppressants (medicines which reduce the defence mechanism of the body) used for the treatment of auto-immune disorders or following transplant surgery (e.g. ciclosporin),

-              tacrolimus (used to control your body’s immune response, enabling your body to accept the transplanted organ)

-              trimethoprim (for the treatment of infections),

-              simvastatin (cholesterol loweringmedicine),

-              medicines, which is most often used to treat diarrhoea (racecadotril) or avoid rejection of transplanted organs (sirolimus, everolimus, temsirolimus and other drugs belonging to the class of so-called mTor inhibitors). See section “Warnings and precautions”

Vidonorm with food, drink and alcohol

Vidonorm should be taken before a meal.

Grapefruit juice and grapefruit should not be consumed by people who are taking Vidonorm. 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 Vidonorm.

Drinking alcohol with Vidonorm may make you feel dizzy or light-headed. You should check with

your doctor if taking alcohol during treatment is possible for you.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally advise you to stop taking Vidonorm before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Vidonorm. Vidonorm is not recommended in early pregnancy, and must not be taken when you are more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breast-feeding

Tell your doctor if you are breast-feeding or about to start breast-feeding. Vidonorm is not recommended for mothers who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely.

Driving and using machines

Vidonorm does not affect alertness but you might experience dizziness, or weakness due to low blood pressure or you might feel sick or have a headache which could affect your ability to drive or operate machinery.


Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Swallow your tablet with a glass of water, preferably at the same time each day, in the morning, before a meal. Your doctor will decide on the correct dose for you. This will normally be one tablet a day.

Vidonorm will usually be prescribed for patients already taking perindopril and amlodipine from separate tablets.

Use in children and adolescents

The efficacy and tolerability of perindopril alone or in combination with amlodipine have not been established in children and adolescents. Therefore, Vidonorm is not recommended for use in children and adolescents.

Use in elderly patients

The combination should be administered with caution, especially in the elderly. Patients should avoid being dehydrated (loosing too much water) and regular medical follow-up should include frequent monitoring of kidney function (creatinine and potassium level).

If you take more Vidonorm than you should

If you take too many tablets, contact your nearest accident and emergency department or tell your doctor immediately. The most likely effect in case of overdose is low blood pressure which can make you feel dizzy or faint. If this happens, lying down with your legs raised can help.

If you forget to take Vidonorm

It is important to take your medicine every day as regular treatment works better. However, if you forget to take a dose of Vidonorm, take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Vidonorm

As the treatment with Vidonorm is usually life-long, you should discuss with your doctor before you

stop taking your tablets.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

 


Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any of the following, stop taking the medicinal product at once and tell your doctor immediately:

-              swelling of the face, lips, mouth, tongue or throat, difficulty in breathing,

-              severe dizziness or fainting due to low bloodpressure,

-              unusually fast or irregular heart-beat, chest pain (angina) or heart attack.

-              weakness of arms or legs, or problems speaking which could be sign of a possible stroke,

-              sudden wheeziness, chest pain, shortness of breath, or difficulty in breathing (bronchospasm),

-              inflamed pancreas which may cause severe abdominal and back pain accompanied with feeling very unwell,

-              yellowing of the skin or eyes (jaundice) which could be a sign of hepatitis,

-              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) or other allergicreactions

-              skin rash which often starts with red itchy patches on your face, arms or legs (erythema multiforme).

Tell your doctor if you notice any of the following side effects: 

Very common side effects (may affect more than 1 in 10 people) Oedema.

Common side effects (may affect up to 1 in 10 people)

Headache, dizziness, vertigo, pins and needles, sleepiness, vision disturbances, palpitation (very fast heart beat), tinnitus (sensation of noises in the ears), flushing (hot or warm feeling in your face), cough, shortness of breath (dyspnoea), gastro-intestinal disorders (nausea, vomiting, abdominal pain, taste disturbances, dyspepsia or difficulty of digestion, diarrhoea, constipation), allergic reactions (such as skin rashes, itching), muscle cramps, ankle swelling, feeling of weakness, feeling of tiredness, low blood pressure.

Uncommon side effects (may affect up to 1 in 100 people)

Change in laboratory parameters (high blood level of potassium reversible on discontinuation, low level of sodium, hypoglycaemia (very low blood sugar level) in case of diabetic patients, increased blood urea, and increased blood creatinine), excess of eosinophils (a type of white blood cells), depression, mood changes, anxiety, sleeplessness, sleep disturbances, trembling, fainting, loss of pain sensation, heart rhythm problems, fast heartbeat, vasculitis (inflammation of blood vessels), sneezing/running nose caused by inflammation of the lining of the nose (rhinitis), bronchospasm (tightening of the chest, wheezing and shortness of breath), dry mouth, angioedema (symptoms such  as wheezing, swelling of the face or tongue), photosensitivity reaction (increased sensitivity of the skin to sun), blistering skin diseases (pemphigoid), hair loss, increased sweating, , red patches on skin, skin discolouration, hives, arthralgia (joint pain), myalgia (muscle pain), back pain, kidney problems, disorder in passing urine, increased need to urinate at night, increased number of times of passing urine, impotence, discomfort or enlargement of the breasts in men, chest pain, pain, malaise, fever, weight increase or decrease, fall.

Rare side effects (may affect up to 1 in 1000 people):

Changes in laboratory parameters: increased level of liver enzymes, high level of serum bilirubin, confusion, psoriasis worsening.

Very rare side effects (may affect up to 1 in 10,000 people):

Changes in blood values such as a lower number of white and red blood cells, lower haemoglobin, lower number of blood platelets, allergic reactions, excess sugar in blood (hyperglycaemia), hypertonia (abnormal increase in muscle tension), neuropathy•(a disorder of the nerves which can cause weakness, tingling or numbness), angina, heart attack, eosinophilic pneumonia (a rare type of pneumonia), stroke, inflammation of pancreas, abdominal bloating (gastritis), swelling of the gums, abnormal liver function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice), erythema multiforme (a skin rash which often starts with red itchy patches on your face, arms or legs), inflammatory skin diseases (exfoliative dermatitis, Stevens-Johnson syndrome), Quincke oedema, acute renal failure.

Not known (frequency cannot be estimated from the available data):

Trembling, rigid posture, mask-like face, slow movements and a shuffling, unbalanced walk.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

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.

 


 

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blisters after “EXP”. The expiry date refers to the last day of that month.

Store in the original package in order to protect from light and moisture. Do not store above 30°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

 


-              The active substances are perindopril tert-butylamine and amlodipine (as amlodipine besilate).

Vidonorm 4 mg / 5 mg tablet contains 4 mg perindopril tert-butylamine and 5 mg amlodipine (as amlodipine besilate).

Vidonorm 8 mg / 5 mg tablet contains 8 mg perindopril tert-butylamine and 5 mg amlodipine (as amlodipine besilate).

Vidonorm 4 mg / 10 mg tablet contains 4 mg perindopril tert-butylamine and 10 mg amlodipine (as amlodipine besilate).

Vidonorm 8 mg / 10 mg tablet contains 8 mg perindopril tert-butylamine and 10 mg amlodipine (as amlodipine besilate).

-              The other ingredients are cellulose, microcrystalline; polacrilin potassium; silica, hydrophobic colloidal; magnesium stearate.


Vidonorm 4 mg / 5 mg tablet: White or almost white, round, flat tablets of 8 mm. Engraving on one side: “CH3”, other side is without engraving. Vidonorm 8 mg / 5mg tablet: White or almost white, round, flat tablets of 8 mm. Engraving on one side: “CH4”, other side is without engraving. Vidonorm 4 mg / 10 mg tablet: White or almost white, round, flat tablets of 11 mm. Engraving on one side: “CH5”, other side is without engraving. Vidonorm 8 mg / 10 mg tablet: White or almost white, round, flat tablets of 11 mm. Engraving on one side: “CH6”, other side is without engraving. 30 tablets are in PA/Aluminium/PVC / Aluminium blister and carton box.

Marketing Authorization Holder:

AJA Pharmaceutical Industries Company, Ltd. Hail, 55414  Saudi Arabia

Tel.: 00966112687900

Fax: 00966112687911

 

Manufacturer :

GEDEON RICHTER POLSKA Sp. z o.o.

ul. ks. J. Poniatowskiego 5

05-825 Grodzisk Mazowiecki

Poland


This leaflet was last revised in 6/2018
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

يوصف فيدونورم لعلاج ارتفاع ضغط الدم و/أو لعلاج مرض الشرايين التاجية المستقر (وهي حالة يقل فيها او يتعطل تدفق الدم إلى عضلة القلب).

 

بالنسبة للمرضى الذين يستعملون أقراص "بيريندوبريل" وأقراص "املوديبين" منفصلة يمكنهم بدلا من ذلك استعمال قرص واحد من فيدونورم.

 

فيدونورم هو منتج يتكون من مادتين فعالتين هما: "بيريندوبريل" و "أملوديبين"

"بيريندوبريل" هو أحد معطلات انزيم تحويل انجيوتنسين (ACE)، و"أملوديبين" هو أحد معطلات قناة الكالسيوم (والذي ينتمي إلى مجموعة من الأدوية تسمى "البيريدينات ثنائية الهيدرو"). وهما معاً يعملان على توسعة وإرخاء الأوعية الدموية حتى يتدفق الدم خلالها بسهولة اكثر ويسهل على القلب الحفاظ على ضخ وتدفق الدم بصورة جيدة.

لا تتناول فيدونورم في الحالات التالية:

-      إذا كانت لديك حساسية لـ "بيريندوبريل" أو لأي من معطلات انزيم تحويل انجيوتنسين (ACE) الأخرى ك أو حساسية لـ"املوديبين" أو أي من مضادات قناة الكالسيوم  الأخرى، او لأي من مكونات هذا الدواء الأخرى (المدرجة في الفقرة رقم-6). وقد يكون ذلك على شكل حكة شديدة او طفح شديد بالجلد، أو احمرار الجلد، او صعوبة في التنفس.

-      بالنسبة للنساء في حالة الحمل لأكثر من 3 شهور (ومن الأفضل تجنب فيدونورم في فترة الحمل المبكرة (انظر الفقرة الخاصة بالحمل).

-      إذا كنت قد اصبت بأعراض الأزيز التنفسي، او تورم (انتفاخ) الوجه او اللسان، أو حكة شديدة او طفح شديد بالجلد، عند استعمال أي من معطلات انزيم تحويل انجيوتنسين (ACE)؛ أو إذا كنت أنت أو أحد أفراد الأسرة قد اصبتم في اوقات او ظروف اخرى بتلك الأعراض والتي تسمى(الوذمة الوعائية).

-      إذا كنت تعاني من الصدمة القلبية  (وهي التي يصبح فيها القلب غير قادر على ضخ كميات كافية من الدم إلى الجسم). أو إذا كنت تعاني من ضيق في الشريان الأورطي (ضيق في الشريان الرئيسي الذي يمر عبره الدم الخارج من القلب).

-      إذا كان لديك انخفاض شديد في ضغط الدم (انخفاض الضغط الشديد). 

-      إذا كنت تعاني من فشل القلب بعد الإصابة باحتشاء حاد في عضلة القلب

-       إذا كنت مصاباً بمرض السكري او قصور في عمل الكلى وتعالج بدواء خافض لضغط الدم يحتوي على "اليسكيرين".

 

تحذيرات واحتياطات:

يجب عليك ابلاغ الطبيب او الصيدلي او احد من طاقم التمريض قبل استعمال فيدونورم في أي من الحالات التالية:

 

-      إذا كنت تعاني من اعتلال عضلة القلب التضخمي (مرض في عضلة القلب)، او ضيق في الشريان الكلوي (ضيق في الشريان الذي يورد الدم إلى الكليتين).

-      إذا كنت تعاني من أي مشاكل أخرى في القلب

-      إذا كنت تعاني من ارتفاع شديد في ضغط الدم (نوبة حادة من ارتفاع ضغط الدم).

-      إذا كنت تعاني من مشاكل بالكبد.

-      إذا كنت تعاني من مشاكل بالكلى.

-      إذا كنت تعاني من مرض الكولاجين الوعائي (مرض يصيب الأنسجة الرابطة) مثل مرض الذؤبة الحماوية العامة او مرض التصلب العصيدي الجلدي.

-      إذا كنت مصاباً بمرض السكري.

-      إذا كنت تتبع حمية غذائية منخفضة الملح وتستعمل بدائل الملح أو المكملات الغذائية التي تحتوي على البوتاسيوم (من الضروري ان يكون مستوى البوتاسيوم بالدم ضمن الحدود الطبيعية).

-      إذا كان اصلك من العرق الأسود حيث ان معطلات انزيم تحويل انجيوتنسين (ACE) قد تكون اقل فعالية في خفض الضغط ولكنك قد تصبح أكثر عرضة للإصابة بالوذمة الوعائية.

-      إذا كنت كبير السن.

-      بالنسبة للمرأة إذا كانت مرضعة.

-      إذا كنت تستعمل أيا من الأدوية المذكورة ادناه والتي تستعمل لعلاج ارتفاع ضغط الدم:

·      احد معطلات مستقبلات أنزيم انجيوتنسين-2 "ARBs" والمعروفة أيضا باسم السارتانات (على سبيل المثال فالسارتان، تيلميسارتان، اربيسارتان) وبشكل خاص اذا كنت تعاني مشاكل في الكلى مرتبطة بمرض السكري.

·      اليسكيرين.

وقد يقرر الطبيب إجراء بعض الفحوصات والتحاليل على فترات منتظمة والتي تشمل وظائف الكلى وضغط الدم ونسبة املاح الدم (مثل البوتاسيوم).

 

-      إذا كنت تستعمل أياً من الأدوية المذكورة أدناه سوف تزيد لديك مخاطر الإصابة بالوذمة الوعائية:

·      ريسيكادوتريل (يستعمل لعلاج الإسهال).

·      سيروليماس، ايفروليماس، تمسيروليماس أو أي ادوية اخرى من مجموعة الأدوية المسماة "مثبطات ام-تور" (التي تستخدم لمنع رفض الجسم للعضو المزروع).

 

بالنسبة للنساء إذا كانت المرأة حاملاً او تعتقد أنها حامل أو تخطط لحدوث الحمل يجب عليها استشارة الطبيب قبل استعمال هذا الدواء. ولا ينصح باستعمال فيدونورم في مراحل الحمل المبكرة ويجب عدم استعماله في حالة الحمل لأكثر من 3 شهور حيث انه قد يسبب اضرارا خطيرة للجنين اذا استخدم في هذه المرحلة من الحمل (انظر الفقرة بعنوان: "الحمل").

 

وانظر ايضا الفقرة بعنوان: "لا تستعمل فيدونورم".

 

إذا كنت تستعمل فيدونورم يجب عليك التحدث إلى الطبيب أو أي من افراد الفريق الطبي في الحالات التالية:

-      إذا كنت ستعطى احد ادوية التخدير و/او ستخضع لعملية جراحية رئيسية.

-      إذا كنت تعاني او تعرضت حديثا لمشكلة التقيؤ.

-     إذا كنت ستخضع لجلسات العلاج المسمى "ال دي ال افريزس" (وهي جلسات يتم فيها فصل الكولسترول من الدم بواسطة جهاز خاص والتخلص منه).

-     إذا كنت تستعمل ادوية لتخفيف الحساسية الناتجة عن لسعات النحل او الزنابير.

 

الأطفال والمراهقون:

لا ينصح بإعطاء فيدونورم للأطفال والمراهقين.

                                            

الأدوية الأخرى و فيدونورم:

يرجى استشارة الطبيب أو الصيدلي إذا كنت تستعمل او استعملت حديثا او يتوقع ان تستخدم أي أدوية أخرى.

ويمكن ان يقوم الطبيب بتعديل الجرعة و/أو اتخاذ تدابير واحتياطات أخرى في الحالات التالية":

 

إذا كنت تستعمل ادوية اخرى خافضة لضغط الدم بما فيها إي من معطلات مستقبل انجيوتنسين-2 (ARB) أو اليسكيرين (انظر أيضا الفقرة تحت عنوان "لا تستعمل فيدونورم" والفقرة الأخرى بعنوان "تحذيرات واحتياطات")؛ أو كنت تستخدم مدرات البول (ادوية تزيد من افراز البول بواسطة الكلى).

 

ومن الضروري تجنب استخدام فيدونورم مع أيٍ من الأدوية التالية:

 

-      ليثيوم (المستخدم لعلاج الذهان أو الاكتئاب).

-      استراموستين (الذي يستخدم لعلاج السرطان).

-      مدرات البول التي تحافظ على البوتاسيوم (مثل سبايرونولاكتون، ترايامتيرين)، وكذلك مستحضرات تزويد البوتاسيوم أو بدائل الملح التي تحتوي على البوتاسيوم.

 

إن العلاج باستخدام فيدونورم يمكن أن يتأثر بالأدوية الأخرى؛ وقد يقرر الطبيب تغيير الجرعات و/أو اتخاذ تدابير اخرى.

ويجب عليك ابلاغ الطبيب اذا كنت تستعمل أياً من الأدوية التالية حيث ان ذلك يتطلب توخي العناية والحرص بشكل خاص:

-      معطلات بيتا المستخدمة لعلاج فشل القلب (مثل بيزوبرولول، كارفيديلول، ميتوبرولول).

-      مضادات الإلتهاب غير الستيرويدية (NSAIDs) مثل (ايبوبروفين) المستخدمة في تسكين الألم أو جرعات عالية من الأسبرين.

-      ادوية علاج مرض السكري (مثل الأنسولين وميتفورمين).

-      الأدوية التي تستخدم لعلاج الإضطرابات النفسية والعقلية مثل الاكتئاب والقلق وانفصام الشخصية (ومن امثلتها مضادات الاكتئاب الحلقية الثلاثية، مضادات الذهان، مضادات الإكتئاب الشبيهة بـ"امبيرامين"، المهدئات العصبية).

-      ألوبيورينول (المستخدم في علاج مرض النقرس).

-      بروكيناميد (المستخدم في علاج عدم انتظام نبض القلب).

-      الأدوية التي تستخدم لتوسعة الأوعية الدموية (مثل فيراباميل او دلتيازيم)، بما فيها النيترات (منتجات توسعة الأوعية الدموية).

-      هيبارين (دواء يستخدم لزيادة سيولة الدم ومنع التجلط).

-      ايفيدرين، نور أدرينالين، أو ادرينالين (التي تستخدم لعلاج انخفاض ضغط الدم، والصدمة، والربو).

-      باكلوفين او دانترولين (بالتنقيط الوريدي) وكلاهما يستخدم لعلاج تصلب العضلات في امراض مثل التصلب العصيدي المتعدد؛ ويستخدم دانترولين لعلاج الحمى الخبيثة اثناء التخدير (وتشمل الأعراض حمى عالية شديدة وتصلب في العضلات).

-      الأدوية التي تستخدم لعلاج الإصابات البكتيرية (مضادات حيوية مثل ريفامبيسين، اريرثرومايسين، كلاريثرومايسين)، او الإصابة بفيروس نقص المناعة (HIV) المسماة مثبطات انزيم البروتيز مثل ريتونافير، اندينافير، نيلفينافير) أو الإصابات الفطرية (مثل كيتوكينازول، اتراكونازول).

-      مضادات التشنج (الصرع) مثل كاربامازيبين، فينوباربيتول، فينوتوين، فوسفينيتوين، بريميدون.

-      معطلات–ألفا التي تستخدم لعلاج تضخم البروستاتا مثل برازوسين، الفيوزوسين، دوكسازوسين، تاميولوسين، تيرازوسين.

-      أميفوستين (المستخدم في تخفيف التأثيرات الجانبية التي تسببها ادوية اخرى او العلاج الإشعاعي والمستخدمة في علاج السرطان).

-      الكورتيكوستيرويدات (التي تستخدم لعلاج حالات مختلفة تشمل الربو والتهاب المفاصل الروماتزمي).

-      المستحضرات العشبية التي تحتوي على عشبة سانت جونز (هيربيكوم بيرفوراتوم).

-      أملاح الذهب خاصة عندما تعطى بالوريد (المستخدمة لعلاج أعراض التهاب المفاصل الروماتيزمي).

-      خافضات المناعة (وهي ادوية تخفض الآليات الدفاعية في الجسم)، وتستخدم لعلاج امراض المناعة الذاتية، أو بعد عمليات زراعة الأعضاء (من امثلتها "سيكلوسبورين").

-      تاكروليماس (المستخدم للسيطرة على الاستجابة المناعية للجسم مما يمكن الجسم من تقبل العضو المزروع).

-      ترايميثوبرين (يستخدم لعلاج الإصابات والعدوى).

-      سمفاستاتين (يستخدم لخفض الكولسترول وبعض انواع الدهون في الدم).

-      ادوية تستخدم عادة لعلاج الإسهال (ريكادوتريل) او منع رفض الجسم للعضو المزروع (سيروليماس، ايفيروليماس، تيمسيروليماس او ادوية أخرى تنتمي إلى مجموعة المواد المسماة "معطلات ام-تور"). انظر الفقرة بعنوان "تحذيرات واحتياطات".

 

فيدونورم مع الأطعمة والمشروبات والكحول:

يجب تناول فيدونورم قبل وجبة طعام. ويجب عدم تناول عصير او فاكهة الجريب فروت من قبل الأشخاص الذين يستعملون فيدونورم، وذلك لأان فاكهة وعصير الجريب فروت يمكن ان تسبب زيادة في مستوى المادة الفعالة "املوديبين" بالدم، مما قد يسبب زيادة غير متوقعة في تأثير فيدونورم الخافض لضغط الدم.

 إن شرب الكحول اثناء استعمال فيدونورم يمكن ان يؤدي إلى شعور بالدوار او الترنح. ويجب استشارة الطبيب حول امكانية شرب الكحول اثناء استعمال علاج فيدونورم.

 

الحمل والإرضاع:

الحمل:

بالنسبة للنساء إذا كانت المرأة حاملاً أو مرضعة او تعتقد أنها حامل أو تخطط لحدوث الحمل يجب عليها استشارة الطبيب قبل استعمال هذا الدواء.

وفي العادة سوف ينصح الطبيب بوقف استعمال فيدونورم قبل حدوث الحمل او فورا عند معرفة حدوث الحمل وسوف ينصح باستعمال دواء آخر بدلا من فيدونورم.

ولا ينصح باستعمال فيدونورم اثناء الحمل ويجب عدم استعماله بعد الشهر الثالث من الحمل حيث انه قد يسبب اضراراً بالغة للجنين إذا استعمل بعد الشهر الثالث من الحمل.

الإرضاع:

يجب على المرأة إبلاغ الطبيب إذا كانت تنوي الإرضاع الطبيعي وقبل ان تبدأ الإرضاع.

لا ينصح باستعمال فيدونورم للأمهات المرضعات وسوف يختار الطبيب دواءً آخر اذا رغبت المرأة في إرضاع الطفل خاصة إذا كان حديث الولادة او انه طفل خداج (مولود قبل اكتمال الحمل).

 

قيادة المركبات وتشغيل الآليات:

لا يؤثر فيدونورم في مستوى الإنتباه او اليقظة، ولكنه قد يسبب الشعور بالدوار او الضعف نظرا لانخفاض ضغط الدم، وقد يؤدي إلى الشعور بالسقم او الغثيان او الصداع مما قد يؤثر في قدرتك على قيادة المركبات أو تشغيل الآليات.


 

https://localhost:44358/Dashboard

 

يجب عليك دائما استعمال هذا الدواء حسب تعليمات الطبيب تماما. وإذا كنت غير متأكد فيجب عليك الإتصال بالطبيب أو الصيدلي.

يجب ابتلاع القرص كاملا مع كوب من الماء ويفضل تناول الدواء في نفس الوقت من كل يوم. والجرعة عادة هي قرص واحد في اليوم.

ويوصف فيدونورم للمرضى الذين يستعملون اقراص "بيرينوبريل" واقراص "املوديبين" كلاً على حدة.

 

الاستعمال لدى الأطفال والمراهقين:

لا تتوفر معلومات عن فعالية او قدرة تحمل او تقبل بيرندوبريل منفردا او جنبا إلى جنب مع أملوديبين لدى الأطفال والمراهقين. ولذلك يجب عدم إعطاء فيدونورم للأطفال والمراهقين.

 

الاستعمال لدى كبار السن:

يجب توخي الحذر والعناية عند اعطاء هذا المزيج لكبار السن. ويجب ان يتنبه هؤلاء المرضى لعدم تعرضهم للجفاف (فقدان الكثير من السوائل)، كما يجب أن تشمل اجراءات المتابعة اجراء تحاليل متكررة لوظائف الكلى (قياس مستويات الكرياتنين والبوتاسيوم في الدم) بصورة منتظمة.

 

إذا تناولت جرعة زائدة من فيدونورم:

إذا تناولت من أقراص فيدونورم زيادة عن وصفة الطبيب فيجب عليك الاتصال بالطبيب فورا. او مراجعة قسم الطوارئ في أقرب مستشفى.

ان زيادة الجرعة ستؤدي غالباً إلى انخفاض ضغط الدم مما يؤدي الى شعور بالدوار. وفي مثل تلك الحالات يفيد المصاب ان يتمدد على ظهره ويرفع رجليه للأعلى.

 

إذا نسيت أن تتناول فيدونورم:

من المهم ان تتناول الدواء يوميا حيث ان اخذ العلاج بانتظام يجعل مفعوله افضل. ولكن إذا نسيت ان تتناول الجرعة المعتادة في وقتها فيجب عليك ان تأخذ الجرعة التالية في وقتها المعتاد. ولا تأخذ جرعة مضاعفة لتعوض التي نسيتها.

 

إذا توقفت عن استعمال فيدونورم:

ان استعمال فيدونورم غالبا يستمر مدى الحياة. ويجب عليك استشارة الطبيب قبل ان تتوقف عن استعمال الدواء. وإذا كانت لديك أي اسئلة او استفسارات حول استعمال هذا الدواء فيجب عليك استشارة الطبيب أو الصيدلي.

هذا الدواء كغيره مكن الأدوية يمكن أن يسبب بعض الآثار الجانبية مع انها لا تحدث لدى جميع الأشخاص.

 

إذا حدثت لك أي من التأثيرات التالية يجب عليك التوقف استعمال فيدونورم وإبلاغ الطبيب على الفور:

-      تورم (انتفاخ) في الوجه والشفتين واللسان أو الحلق وصعوبة في التنفس.

-      دوار شديد او إغماء نتيجة انخفاض ضغط الدم.

-      تسارع أو عدم انتظام نبضات القلب، الأم بالصدر (ذبحة صدرية)، أو نوبة قلبية

-      ضعف بالذراعين او الرجلين أو مشاكل وصعوبات في الكلام مما قد يكون علامات على جلطة دماغية.

-      أزيز تنفسي مفاجئ، الم بالصدر، ضيق بالتنفس، أو صعوبة في التنفس (تشنج الشعب الهوائية).

-      التهاب البنكرياس مما قد ينتج عنه ألم شديد في البطن والظهر مع شعور بالسقم الشديد

-      اصفرار الجلد والعينين (يرقان) مما قد يعني اعراض التهاب الكبد.

-      ردود فعل شديدة بالجلد تشمل الطفح الجلدي الكثيف، احمرار الجلد، في كل انحاء الجسم، حكة شديدة بالجلد، ظهور نفط، تقشر وتورم الجلد، التهاب الأغشية المخاطية  (متلازمة ستيفن-جونسون)، او ردود فعل حساسية أخرى.

-      طفح جلدي يبدأ عادة على شكل بقع محمرة بالوجه والذراعين او الرجلين (الطفح الإحمراري عديد التشكل).

يجب عليك ابلاغ الطبيب إذا لاحظت أياً من التأثيرات الجانبية التالية:

 

تأثيرات جانبية شائعة جداً(يمكن ان تصيب ما يزيد عن  1 من بين كل 10 اشخاص):

تورم أوديمي (وذمة).

 

تأثيرات جانبية شائعة (يمكن ان تصيب لغاية 1 من بين كل 10 اشخاص):

صداع، دوار، ترنح، تنميل مثل وخز الإبر، نعاس، اضطرابات في النظر، خفقان بالقلب (تسارع في نبضات القلب)، طنين في الأذن (احساس بأصوات مشوشة في الأذن)، حماويةالوجه (احساس بالسخونة في الوجه)، سعال، ضيق في التنفس، اضطرابات بالمعدة والأمعاء (غثيان، تقيؤ، الم في البطن، اضطرابات في التذوق، عسر الهضم، اسهال، إمساك)، ردود فعل حساسية (مثل الطفح الجلدي والحكة)، تقلصات وتشنجات عضلية، تورم الكاحل، شعور بالضعف، شعور بالتعب، انخفاض ضغط الدم.

 

تأثيرات غير شائعة (يمكن ان تصيب لغاية  1 من بين كل 100 شخص):

تغيرات في نتائج تحاليل الدم (ارتفاع مستوى البوتاسيوم يزول عند وقف استعمال الدواء، انخفاض مستوى الصوديوم بالدم، انخفاض شديد في مستوى السكر بالدم، وفي حالة مرضى السكري ارتفاع مستوى البولينا بالدم، وارتفاع مستوى الكرياتنين بالدم)، زيادة اعداد كريات الدم البيضاء الحمضية، اكتئاب، تقلبات في المزاج، قلق، نعاس، اضطرابات في النوم، ارتجاف، إغماء، فقدان الإحساس بالألم، مشاكل في ايقاع وانتظام ضربات القلب، تسارع النبض، التهاب الأوعية الدموية، عطاس /رشح من الأنف بسبب التهاب الغشاء المبطن للأنف (التهاب الأنف)، تشنجات في الشعب الهوائية (ضيق بالصدر، أزيز تنفسي وضيق بالتنفس)، جفاف الفم، وذمة وعائية (تشمل أعراضها ازيز تنفسي، تورم الوجه أو اللسان)، ردة فعل حساسية للضوء (زيادة في حساسية الجلد لأشعة الشمس)، تنفط بالجلد، تساقط الشعر، زيادة التعرق، بقع حمراء على الجلد، تغير لون الجلد، شرى (حكة مع حرقان بالجلد) اوجاع بالمفاصل، اوجاع بالعضلات، الم بالظهر، مشاكل في الكلى، اضطرابات في التبول، زيادة الرغبة في التبول اثناء الليل، زيادة وتيرة (معدل تكرار) التبول، ضعف القدرة الجنسية، مضايقة أو زيادة حجم الثديين لدى الرجال، الم بالصدر، إعياء، حمى زيادة أو نقص الوزن، تعثر وسقوط.

 

تأثيرات نادرة (يمكن ان تصيب لغاية  1 من بين كل 1000 شخص):

تغيرات في نتائج تحاليل الدم: ارتفاع مستويات انزيمات الكبد، ارتفاع مستوى البيليروبين بالدم، ارتباك وتشوش تفاقم مرض الصدفية.

 

تأثيرات نادرة جداً (يمكن ان تصيب لغاية  1 من بين كل 10000 شخص):

 

تغيرات في نتائج تحاليل مكونات الدم مثل انخفاض تعداد كريات الدم البيضاء والحمراء، انخفاض مستوى الهيموجلوبين، انخفاض اعداد الصفائح الدموية؛ ردود فعل حساسيةارتفاع مستوى السكر في الدم (فرط الجلوكوز)، زيادة غير طبيعية في توتر العضلات، اعتلالات عصبية (خلل في الأعصاب يمكن ان يسبب الضعف أو الخدر أو التنميل، ذبحة صدرية، نوبة قلبية، التهاب رئوي ايزينوفيلي (نوع نادر من الالتهابات الرئوية)، جلطة دماغية، التهاب البنكرياس، انتفاخ البطن (التهاب المعدة)، تورم اللثة، خلل في وظائف الكبد، التهاب الكبد، اصفرار الجلد(يرقان)، حماوية احمرارية عديدة التشكل (طفح جلدي يبدأ على شكل بقع حمراء مع حكة تظهر على الوجه أو الذراعين أو الرجلين)، مرض التهابي بالجلد (التهاب الجلد التقشري، متلازمة ستيفن – جونسون)وذمة كوينكي، فشل كلوي حاد.

 

تأثيرات غير معروفة (لا يمكن تقدير معدلات الحدوث من واقع البيانات المتوفرة):

ارتجاف، تصلب في وضعية الجسم، وجه شبيه بالقناع، بطء الحركة والتلكؤ، مشية غير متوازنة.

الإبلاغ عن الآثار الجانبية:

إذا ظهرت لديك أي من التأثيرات الجانبية فيجب أن تبادر بالتحدث إلى الطبيب أو الصيدلي أو الممرضة. وتشمل تلك الأعراض اي تأثيرات محتملة اخرى لم يرد ذكرها في هذه النشرة.

للإبلاغ عن أي تأثيرات جانبية:

·      المملكة العربية السعودية

المركز الوطني للمراقبة الصيدلانية وسلامة العقاقير (ان بي سي)

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·       هاتف الإتصال المجاني: 8002490000

·       بريد الكتروني: npc.drug@sfda.gov.sa

·      الموقع على الشبكة: www.sfda.gov.sa/npc

 

·      دول مجلس التعاون الخليجي الأخرى:

يرجى الإتصال بالسلطات المختصة في كل بلد.

 

 

احفظ هذا الدواء بعيدا عن مرأى ومتناول الأطفال.

 

لا تستعمل هذا الدواء بعد تاريخ انتهائه المطبوع على الشرائح البثورية وعلى العلبة بعد الحروف الإنجليزي: "EXP". ويشير تاريخ انتهاء الصلاحية إلى آخر يوم في ذلك الشهر.

 

هذا الدواء لا يتطلب درجات حرارة خاصة للتخزين.

 

يجب تخزينه في العبوات الأصلية لحمايته من الضوء والرطوبة.

لا تلقي بأي ادوية في شبكة الصرف الصحي او النفايات المنزلية. اسأل الصيدلي عن الطرق السليمة للتخلص من الأدوية لم تعد بحاجة لاستخدامها. فهذه الإجراءات تساعد في حماية البيئة.

 

-      المواد الفعالة هي "بريندوبريل تيرتبيوتايل أمين" و"أملودبين" (على هيئة بيسايليت).

 

فيدونورم 4 ملجم/5 ملجم:

كل قرص يحتوي على 4 ملجم "بريندوبريل تيرتبيوتايل أمين" و5 ملجم "أملودبين" (على هيئة بيسايليت).

 

فيدونورم 8 ملجم/5 ملجم:

كل قرص يحتوي على 8 ملجم "بريندوبريل تيرتبيوتايل أمين" و10 ملجم "أملودبين" (على هيئة بيسايليت).

 

فيدونورم 4 ملجم/10 ملجم:

كل قرص يحتوي على 4 ملجم "بريندوبريل تيرتبيوتايل أمين" و10 ملجم "أملودبين" (على هيئة بيسايليت).

 

فيدونورم 8 ملجم/10 ملجم:

كل قرص يحتوي على 8 ملجم "بريندوبريل تيرتبيوتايل أمين" و10 ملجم "أملودبين" (على هيئة بيسايليت).

 

-    المكونات الأخرى هي:

سليولوز، مايكروكريستلين، بولاكريلين بوتاسيوم، سيليكا، كولويدال لامائي، مغنيسيوم ستيريت.

فيدونورم 4 ملجم/5 ملجم:

أقراص دائرية مسطحة بيضاء أو تقريبا بيضاء اللون بقطر 8 ملم، مكتوب بخط غائر على احد الوجهين الرمز "CH3" والوجه الآخر لا يوجد عليه أي كتابة.

 

فيدونورم 8 ملجم/5 ملجم:

أقراص دائرية مسطحة بيضاء أو تقريبا بيضاء اللون بقطر 8 ملم، مكتوب بخط غائر على احد الوجهين الرمز "CH4" والوجه الآخر لا يوجد عليه أي كتابة.

فيدونورم 4 ملجم/10 ملجم:

أقراص دائرية مسطحة بيضاء أو تقريبا بيضاء اللون بقطر 11 ملم، مكتوب بخط غائر على احد الوجهين الرمز "CH5" والوجه الآخر لا يوجد عليه أي كتابة.

 

فيدونورم 8 ملجم/10 ملجم:

أقراص دائرية مسطحة بيضاء أو تقريبا بيضاء اللون بقطر 11 ملم، مكتوب بخط غائر على احد الوجهين الرمز "CH6" والوجه الآخر لا يوجد عليه أي كتابة.

 

تحتوي العبوة على 30 قرصاً في شرائح من مواد "بي اي/بي في سي- الومنيوم"  معبأة في علبة من الورق المقوى (الكرتون).

 

شركة أجا للصناعات الدوائية المحدودة

حائل 55414، المملكة العربية السعودية

هاتف: 00966112687900

فاكس: 00966112687911

المصنع:

جيديون ريختر بولسكا اس بي زوو

يو ال. كي اس.بونياتوسكيجو 5

05-825 جرودسيك مازويكي

بولندا

تمت مراجعة هذه النشرة آخر مرة بتاريخ: 6/2018
 Read this leaflet carefully before you start using this product as it contains important information for you

Vidonorm 4 mg/5 mg tablets Vidonorm 8 mg/5 mg tablets Vidonorm 4 mg/10 mg tablets Vidonorm 8 mg/10 mg tablets

Vidonorm 4 mg / 5 mg tablet: Each tablet contains 4 mg perindopril tert-butylamine and 5 mg amlodipine (as amlodipine besilate). Vidonorm 8 mg / 5 mg tablet: Each tablet contains 8 mg perindopril tert-butylamine and 5 mg amlodipine (as amlodipine besilate). Vidonorm 4 mg / 10 mg tablet: Each tablet contains 4 mg perindopril tert-butylamine and 10 mg amlodipine (as amlodipine besilate). Vidonorm 8 mg / 10 mg tablet: Each tablet contains 8 mg perindopril tert-butylamine and 10 mg amlodipine (as amlodipine besilate). For the full list of excipients, see section 6.1.

Tablet. Vidonorm 4 mg / 5 mg tablet: White or almost white, round, flat tablets of 8 mm. Engraving on one side: “CH3”, other side is without engraving. Vidonorm 8 mg / 5 mg tablet: White or almost white, round, flat tablets of 8 mm.. Engraving on one side: “CH4”, other side is without engraving. Vidonorm 4 mg / 10 mg tablet: White or almost white, round, flat tablets of 11 mm.. Engraving on one side: “CH5”, other side is without engraving. Vidonorm 8 mg / 10 mg tablet: White or almost white, round, flat tablets of 11 mm.. Engraving on one side: “CH6”, other side is without engraving.

Vidonorm is indicated as substitution therapy for treatment of essential hypertension and/or stable coronary artery disease, in patients already controlled with perindopril and amlodipine given concurrently at the same dose level.


Posology

One tablet per day as a single dose.

The fixed dose combination is not suitable for initial therapy.

If the change of the dosage is required, it should be carried out by individual titration using the mono component products.

Patients with renal impairment and older people (see sections 4.4 and 5.2).

Elimination of perindoprilat is decreased in older people and in patients with renal failure. Therefore, the usual medical follow-up will include frequent monitoring of creatinine and potassium.

Vidonorm can be administered in patients with Clcr ≥60ml/min, and is not suitable for patients with Clcr <60ml/min. In these patients, an individual dose titration with the monocomponents is recommended.

Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment. Amlodipine is not dialysable.

Patients with hepatic impairment: see sections 4.4 and 5.2.

A dosage regimen for patients with hepatic impairment has not been established. Therefore, Vidonorm should be administered with caution.

Paediatric population

Vidonorm should not be used in children and adolescents as the efficacy and tolerability of perindopril alone or in combination with amlodipine have not been established in children and adolescents.

Method of administration

Oral route. Preferably to be taken in the morning and before a meal.


Linked to perindopril:   -              Hypersensitivity to perindopril or to any other ACEinhibitor, -              History of angioedema associated with previous ACE inhibitor therapy, -              Hereditary or idiopathic angioedema, -              Second and third trimesters of pregnancy (see sections 4.4 and 4.6), -              Concomitant use of Vidonorm with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.4, 4.5 and 5.1). Linked to amlodipine:   -              Hypersensitivity to amlodipine or to any otherdihydropyridines, -              Severe hypotension, -              Shock, including cardiogenic shock, -              Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis), -              Haemodynamically unstable heart failure after acute myocardial infarction. Linked to Vidonorm:   All contraindications related to each monocomponent, as listed above, should apply also to the fixed combination of Vidonorm. -              Hypersensitivity to any of the excipients listed in section 6.1.

 

All warnings related to each monocomponent, as listed below, should apply also to the fixed combination of Vidonorm.

 

Linked to perindopril

 

Stable coronary artery disease:

If an episode of unstable angina pectoris (major or not) occurs during the first month of perindopril treatment, a careful appraisal of the benefit/risk should be performed before treatment continuation.

 

Hypotension:

 

ACE inhibitors may cause a fall in blood pressure. Symptomatic hypotension is seen rarely in uncomplicated hypertensive patients and is more likely to occur in patients who have been volume- depleted e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting, or who have severe renin-dependent hypertension (see sections 4.5 and 4.8). In patients with symptomatic heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be closely monitored (see sections 4.2 and 4.8). Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

 

If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of sodium chloride 9 mg/ml (0.9%) solution. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.

In some patients with congestive heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with perindopril.

This effect is anticipated and is usually not a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose or discontinuation of perindopril may be necessary.

 

Aortic and mitral valve stenosis / hypertrophic cardiomyopathy:

As with other ACE inhibitors, perindopril should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy.

 

Renal impairment:

In cases of renal impairment (creatinine clearance < 60 ml/min) the initial perindopril dosage should be adjusted according to the patient's creatinine clearance (see section 4.2) and then as a function of the patient's response to treatment. Routine monitoring of potassium and creatinine are part of normal medical practice for these patients (see section 4.8).

 

In patients with symptomatic heart failure, hypotension following the initiation of therapy with ACE inhibitors may lead to some further impairment in renal function. Acute renal failure, usually reversible, has been reported in this situation.

 

In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, who have been treated with ACE inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen. This is especially likely in patients with renal insufficiency. If renovascular hypertension is also present there is an increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started under close medical supervision with low doses and careful dose titration. Since treatment with diuretics may be a contributory factor to the above, they should be discontinued and renal function should be monitored during the first weeks of perindopril therapy.

 

Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when perindopril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or perindopril may be required.

 

Haemodialysis patients:

Anaphylactoid reactions have been reported in patients dialysed with high flux membranes, and  treated concomitantly with an ACE inhibitor. In these patients consideration should be given to using a different type of dialysis membrane or different class of antihypertensive agent.

 

Kidney transplantation:

 

There is no experience regarding the administration of perindopril in patients with a recent kidney transplantation.

 

Hypersensitivity/Angioedema:

Angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx has been reported rarely in patients treated with ACE inhibitors, including perindopril (see section 4.8). This may occur at any time during therapy. In such cases, perindopril should promptly be discontinued and appropriate monitoring should be initiated and continued until complete resolution of symptoms has occurred. In those instances where swelling was confined to the face and lips the condition generally resolved without treatment, although antihistamines have been useful in relieving symptoms.

 

Angioedema associated with laryngeal oedema may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, emergency therapy should be administered promptly. This may include the administration of adrenaline and/or the maintenance of a patent airway. The patient should be under close medical supervision until complete and sustained resolution of symptoms has occurred.

 

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see section 4.3).

 

Intestinal angioedema has been reported rarely in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan, or ultrasound or at surgery and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

 

Concomitant use of mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus)

Patients taking concomitant mTOR inhibitor (e.g. sirolimus, everolimus, temsirolimus) therapy may be at increased risk for angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment) (see section 4.5).

 

Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis:

Rarely, patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulfate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.

 

Anaphylactic reactions during desensitisation:

Patients receiving ACE inhibitors during desensitisation treatment (e.g. hymenoptera venom) have experienced anaphylactoid reactions. In the same patients, these reactions have been avoided when the ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

 

Hepatic failure:

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up (see section 4.8).

 

Neutropenia/Agranulocytosis/Thrombocytopenia/Anaemia:

Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia occurs rarely.

 

Perindopril should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function. Some of these patients

 

developed serious infections, which in a few instances did not respond to intensive antibiotic therapy. If perindopril is used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection (e.g. sore throat, fever).

 

Race:

ACE inhibitors cause a higher rate of angioedema in black patients than in non-black patients.

As with other ACE inhibitors, perindopril may be less effective in lowering blood pressure in black people than in non-blacks, possibly because of a higher prevalence of low-renin states in the black hypertensive population.

 

Cough:

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non- productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

 

Surgery/Anaesthesia:

In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, perindopril may block angiotensin II formation secondary to compensatory renin release. The treatment should be discontinued one day prior to the surgery. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

 

Hyperkalaemia:

Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including perindopril. Risk factors for the development of hyperkalaemia include those with renal insufficiency, worsening of renal function, age (> 70 years), diabetes mellitus, intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis and concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene, or amiloride), potassium supplements or potassium-containing salt substitutes; or those patients taking other drugs associated with increases in serum potassium (e.g. heparin).

 

The use of potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes particularly in patients with impaired renal function may lead to a significant increase in serum potassium. Hyperkalaemia can cause serious, sometimes fatal arrhythmias. If concomitant use of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium (see section 4.5).

 

Diabetic patients:

In diabetic patients treated with oral antidiabetic agents or insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor (see section 4.5).

 

Lithium:

The combination of lithium and perindopril is generally not recommended (see section 4.5).

 

Potassium-sparing drugs, potassium supplements or potassium-containing salt substitutes:

The combination of perindopril and potassium-sparing drugs, potassium supplements or potassium- containing salt substitutes is generally not recommended (see section 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 sections 4.5 and 5.1).

 

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.

 

Pregnancy:

ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

 

Linked to amlodipine:

 

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 (see section 5.1). 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.

 

Hepatic impairment

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

In the elderly increase of the dosage should take place with care (see sections 4.2 and 5.2).

 

Renal impairment

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.

 

Linked to Vidonorm

 

All warnings related to each monocomponent, as listed above, should apply also to the fixed combination of Vidonorm.

 

Precautions for use

 

Interactions

The concomitant use of Vidonorm with lithium, potassium-sparing diuretics or potassium supplements, or dantrolene is not recommended (see section 4.5).


Linked to perindopril

 

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 sections 4.3, 4.4 and 5.1).

 

Racecadotril

 

ACE inhibitors (e.g. perindopril) are known to cause angioedema. This risk may be elevated when used concomitantly with racecadotril (a drug used against acute diarrhoea).

 

mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus)

Patients taking concomitant mTOR inhibitor therapy may be at increased risk for angioedema (see section 4.4).

 

Drugs inducing hyperkalaemia

Some drugs or therapeutic classes may increase the occurrence of hyperkalaemia: aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin-II receptors antagonists, NSAIDs, heparins, immunosuppressant agents such as ciclosporin or tacrolimus, trimethoprim. The combination of these drugs increases the risk of hyperkalaemia.

 

Concomitant use not recommended (see section 4.4):

 

Estramustine:

Risk of increased adverse effects such as angioneurotic oedema (angioedema).

 

Potassium-sparing diuretics (e.g. triamterene, amiloride), potassium salts:

Hyperkalaemia (potentially lethal), especially in conjunction with renal impairment (additive hyperkalaemic effects).

The combination of perindopril with the above-mentioned drugs is not recommended (see section 4.4). If concomitant use is nonetheless indicated, they should be used with caution and with frequent monitoring of serum potassium. For use of spironolactone in heart failure, see below.

 

Lithium:

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Use of perindopril with lithium is not recommended, but if the combination proves necessary, careful monitoring of serum lithium levels should be performed (see section 4.4).

 

Concomitant use which requires special care:

 

Antidiabetic agents (insulins, oral hypoglycaemic agents):

Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicines (insulins, oral hypoglycaemic agents) may cause an increased blood-glucose lowering effect with risk of hypoglycaemia.

This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment.

 

Baclofen:

Increased antihypertensive effect. Monitor blood pressure and adapt antihypertensive dosage if necessary.

 

Non-potassium-sparing diuretics:

Patients on diuretics, and especially those who are volume and/or salt depleted, may experience excessive reduction in blood pressure after initiation of therapy with an ACE inhibitor. The possibility of hypotensive effects can be reduced by discontinuation of the diuretic, by increasing volume or salt intake prior to initiating therapy with low and progressive doses of perindopril.

 

In arterial hypertension, when prior diuretic therapy can have caused salt/volume depletion, either the diuretic must be discontinued before initiating the ACE inhibitor, in which case a non-potassium- sparing diuretic can be thereafter reintroduced or the ACE inhibitor must be initiated with a low dosage and progressively increased.

 

In diuretic-treated congestive heart failure, the ACE inhibitor should be initiated at a very low dosage, possibly after reducing the dosage of the associated non-potassium-sparing diuretic.

 

In all cases, renal function (creatinine levels) must be monitored during the first few weeks of ACE inhibitor therapy.

 

Potassium-sparing diuretics (eplerenone, spironolactone):

With eplerenone or spironolactone at doses between 12.5 mg to 50 mg by day and with low doses of ACE inhibitors:

In the treatment of class II-IV heart failure (NYHA) with an ejection fraction < 40%, and previously treated with ACE inhibitors and loop diuretics, risk of hyperkalaemia, potentially lethal, especially in case of non-observance of the prescription recommendations on this combination.

Before initiating the combination, check the absence of hyperkalaemia and renal impairment. A close monitoring of the kalaemia and creatinaemia is recommended in the first month of the treatment once a week at the beginning and, monthly thereafter.

 

Non-steroidal anti-inflammatory medicinal products (NSAIDs) including aspirin ≥ 3 g/day:

When ACE-inhibitors are administered simultaneously with non-steroidal anti-inflammatory drugs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs), attenuation of the antihypertensive effect may occur. Concomitant use of ACE-inhibitors 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.

 

Concomitant use which requires some care:

 

Antihypertensive agents and vasodilators:

Concomitant use of these agents may increase the hypotensive effects of perindopril. Concomitant use with nitroglycerin and other nitrates, or other vasodilators, may further reduce blood pressure.

 

Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin):

Increased risk of angioedema, due to dipeptidyl peptidase IV (DPP-IV) decreased activity by the gliptin, in patients co-treated with an ACE inhibitor.

 

Tricyclic antidepressants/Antipsychotics/Anaesthetics:

Concomitant use of certain anaesthetic medicinal products, tricyclic antidepressants and antipsychotics with ACE inhibitors may result in further reduction of blood pressure (see section 4.4).

 

Sympathomimetics:

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.

 

Gold:

Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including perindopril.

 

Linked to amlodipine

 

Effects of other medicinal products on amlodipine

 

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 resulting in an increased risk of hypotension. The clinical translation of these PK variations may be more pronounced in the elderly. Clinical monitoring of patients is recommended and dose adjustment may thus be required. Clarithromycin is an inhibitor of CYP3A4. There is an increased risk of hypotension in patients receiving clarithromycin with

 

amlodipine. Close observation of patients is recommended when amlodipine is co administered with clarithromycin.

 

CYP3A4 inducers:

There is no data available regarding the effect of CYP3A4 inducers on amlodipine. The concomitant use of CYP3A4 inducers (e.g., rifampicin, hypericum perforatum) may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

 

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.

 

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

 

The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other medicinal products with antihypertensive properties.

In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin or warfarin.

 

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.

 

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.

 

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 in patients on amlodipine to 20 mg daily.

 

Linked to Vidonorm

 

Concomitant use which requires special care:

 

Baclofen:

Potentiation of antihypertensive effect. Monitoring of blood pressure and renal function, and dose adjustment of the antihypertensive if necessary.

 

Concomitant use to be taken into consideration:

 

Antihypertensive agents (such as beta-blockers) and vasodilators:

Concomitant use of these agents may increase the hypotensive effects of perindopril and amlodipine. Concomitant use with nitroglycerine and other nitrates or other vasodilators, may further reduce blood

 

pressure and therefore should be considered with caution.

 

Corticosteroids, tetracosactide:

Reduction in antihypertensive effect (salt and water retention due to corticosteroids).

 

Alpha-blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin): Increased antihypertensive effect and increased risk of orthostatic hypotension.

 

Amifostine:

May potentiate the antihypertensive effect of amlodipine.

 

Tricyclic antidepressants/antipsychotics/anaesthetics:

Increased antihypertensive effect and increased risk of orthostatic hypotension.

 


Given the effects of the individual components in this combination product on pregnancy and lactation:

 

Vidonorm is not recommended during the first trimester of pregnancy. When a pregnancy is planned or confirmed, the switch to an alternative treatment should be initiated as soon as possible.

Vidonorm is contraindicated during the second and third trimesters of pregnancy.

 

Vidonorm is not recommended during lactation. A decision should therefore be made whether to discontinue nursing or to discontinue Vidonorm taking account the importance of this therapy for the mother.

 

Pregnancy:

 

Linked to perindopril

 

The use of ACE inhibitors is not recommended during the first trimester of pregnancy (see section 4.4). The use of ACE inhibitors is contraindicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4).

 

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor 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 ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.

 

Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).

 

Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.

 

Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension, (see sections 4.3 and 4.4).

 

Linked to amlodipine

 

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.

 

Breastfeeding:

 

Linked to perindopril

 

Because no information is available regarding the use of perindopril during breastfeeding, perindopril is not recommended and alternative treatments with better established safety profiles during breast- feeding are preferable, especially while nursing a newborn or preterm infant.

 

Linked to amlodipine

 

It is not known whether amlodipine is excreted in breast milk.

 

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:

 

Linked to perindopril

 

There was no effect on reproductive performance or fertility.

 

Linked to amlodipin

 

Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated with 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).

 


No studies on the effects of Vidonorm on the ability to drive and use machines have been performed. When driving vehicles or operating machines it should be taken into account that occasionally low blood pressure, headache, nausea, dizziness or weariness may occur.

 


 

The following undesirable effects have been observed during treatment with perindopril or amlodipine given separately and ranked under the MedDRA classification by body system and under the following frequency:

 

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); not known (cannot be estimated from the available data).

 

System organ class

Frequency

Adverse reactions

 

 

Amlodipine

Perindopril

Blood and lymphatic system disorders

Uncommon

 

Eosinophilia**

Very rare

Leukocytopenia, Thrombocytopenia

Agranulocytosis or pancytopenia, Haemoglobin decreased and haematocrit decreased, Leucopenia/neutropenia, Haemolytic anaemia in patients with a congenital deficiency of

 

 

 

 

G-6PDH (see section 4.4), Thrombocytopenia

Immune system disorders

Very rare

Allergic reactions

 

Metabolism and nutrition disorders

Uncommon

 

Hypoglycaemia (see sections 4.4 and 4.5)**,

Hyperkalaemia, reversible on discontinuation (see section 4.4)**,

Hyponatraemia**

Very rare

Hyperglycaemia

 

Psychiatric disorders

Uncommon

Depression,

Mood changes (including anxiety),

Insomnia

Mood disturbances, Sleep disorder

Rare

Confusion

 

Nervous system disorders

Common

Somnolence, Dizziness,

Headache (especially at the beginning of the treatment)

Dizziness, Headache, Paraesthesia, Vertigo

Uncommon

Tremor, Dysgeusia, Syncope, Hypoaesthesia, Paraesthesia

Somnolence**, Syncope**

Very rare

Hypertonia, peripheral neuropathy

Confusion

Not known

Extrapyramidal disorder

 

Eye disorders

Common

Visual disturbance (including diplopia)

Visual disturbances

Ear and labyrinth disorders

Common

 

Tinnitus

Uncommon

Tinnitus

 

Cardiac disorders

Common

Palpitations

 

Uncommon

Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation)

Palpitations**, Tachycardia**

Very rare

Myocardial infarction

Angina pectoris (see section 4.4), Arrhythmia,

Myocardial infarction, possibly secondary to excessive hypotension in high risk patients (see section 4.4)

Vascular disorders

Common

Flushing

Hypotension (and effects related to hypotension)

Uncommon

Hypotension

Vasculitis**

Very rare

Vasculitis

Stroke possibly secondary to excessive hypotension in high- risk patients (see section 4.4)

Respiratory,

Common

Dyspnoea

Cough,

 

thoracic and mediastinal disorders

 

 

Dyspnoea

Uncommon

Cough, Rhinitis

Bronchospasm

Very rare

 

Eosinophilic pneumonia, Rhinitis

Gastrointestinal disorders

Common

Abdominal pain, Nausea, Dyspepsia,

Altered bowel habits (including diarrhoea and constipation)

Abdominal pain, Constipation, Diarrhoea, Dysgeusia, Dyspepsia, Nausea, Vomiting

Uncommon

Vomiting, Dry mouth

Dry mouth

Very rare

Pancreatitis, Gastritis,

Gingival hyperplasia

Pancreatitis

Hepatobiliary disorders

Very rare

Hepatitis, Jaundice,

Hepatic enzyme increased*

Hepatitis either cytolytic or cholestatic (see section 4.4)

Skin and subcutaneous tissue disorders

Common

 

Pruritus, Rash

Uncommon

Alopecia, Purpura,

Skin discolouration, Hyperhidrosis, Pruritus,

Rash, Exanthema, Urticaria

Urticaria (see section 4.4), Angioedema of face, extremities, lips, mucous membranes, tongue, glottis and/or larynx (see section 4.4),

Photosensitivity reactions**, Pemphigoid**, Hyperhidrosis,

Rare

 

Psoriasis aggravation

Very rare

Angioedema, Erythema multiforme, Exfoliative dermatitis,

Stevens-Johnson syndrome, Quincke oedema, Photosensitivity

Erythema multiforme

Musculoskeletal and connective tissue disorders

Common

Ankle swelling, Muscle cramps

Muscle cramps

Uncommon

Arthralgia, Myalgia, Back pain

Arthralgia**, Myalgia**

Renal and urinary disorders

Uncommon

Micturition disorder, Nocturia,

Increased urinary frequency

Renal insufficiency

Very rare

 

Acute renal failure

Reproductive system and breast disorders

Uncommon

Impotence, Gynaecomastia

Erectile dysfunction

General disorders and administration

Very common

Oedema

 

 

site conditions

Common

Fatigue, Asthenia

Asthenia

Uncommon

Chest pain, Pain, Malaise

Chest pain**, Malaise**,

Oedema peripheral**, Pyrexia**

Investigations

Uncommon

Weight increased, Weight decreased

Blood urea increased**, Blood creatinine increased**

Rare

 

Blood bilirubin increased, Hepatic enzyme increased

Injury, poisoning and procedural complications

Uncommon

 

Fall**

 

Linked to perindopril

 

** Frequency calculated from clinical trials for adverse events detected from spontaneous report

 

Linked to amlodipine

 

*  Mostly consistent with cholestasis

 

Clinical trials with perindopril:

During the randomised period of the EUROPA study, only serious adverse events were collected. Few patients experienced serious adverse events: 16 (0.3%) of the 6122 perindopril patients and 12 (0.2%) of the 6107 placebo patients. In perindopril-treated patients, hypotension was observed in 6 patients, angioedema in 3 patients and sudden cardiac arrest in 1 patient. More patients withdrew for cough, hypotension or other intolerance on perindopril than on placebo, 6.0% (n=366) versus 2.1% (n=129) respectively.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

 

•  Saudi Arabia:

 
  

The National Pharmacovigilance and Drug Safety Centre (NPC)

·  Fax: +966-11-205-7662

·  Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

·  Toll free phone: 8002490000

·  E-mail: npc.drug@sfda.gov.sa

·  Website: www.sfda.gov.sa/npc

 

o    Other GCC States:

Please contact the relevant competent authority.

 


There is no information on overdosage with Vidonorm in humans.

 

Linked to perindopril

 

Limited data are available for overdose in humans. Symptoms associated with the overdose of ACE inhibitors may include hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, and cough.

The recommended treatment of overdose is intravenous infusion of sodium chloride 9 mg/ml (0.9%) solution. If hypotension occurs, the patient should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered.

Periondopril may be removed from the systemic circulation by haemodialysis (see section 4.4). Pacemaker therapy is indicated for treatment-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored continuously.

 

Linked to amlodipine

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: ACE inhibitors and calcium channel blockers, ATC code: C09BB04

 

Linked to perindopril:

 

Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (Angiotensin Converting Enzyme ACE). The converting enzyme, or kinase, is an exopeptidase that allows conversion of angiotensin I into the vasoconstrictor angiotensin II as well as causing the degradation of the vasodilator bradykinin into an inactive heptapeptide. Inhibition of ACE results in a reduction of angiotensin II in the plasma, which leads to increased plasma renin activity (by inhibition of the negative feedback of renin release) and reduced secretion of aldosterone. Since ACE inactivates bradykinin, inhibition of ACE also results in an increased activity of circulating and local kallikrein- kinin systems (and thus also activation of the prostaglandin system). It is possible that this mechanism contributes to the blood pressure lowering action of ACE inhibitors and is partially responsible for certain of their side effects (e.g. cough).

 

Perindopril acts through its active metabolite, perindoprilat. The other metabolites show no inhibition of ACE activity in vitro.

 

Clinical efficacy and safety Hypertension:

Perindopril is active in all grades of hypertension: mild, moderate, severe; a reduction in systolic and diastolic blood pressures in both supine and standing positions is observed.

Perindopril reduces peripheral vascular resistance, leading to blood pressure reduction. As a consequence, peripheral blood flow increases, with no effect on heart rate.

Renal blood flow increases as a rule, while the glomerular filtration rate (GFR) is usually unchanged. The antihypertensive activity is maximal between 4 and 6 hours after a single dose and is sustained for at least 24 hours: trough effects are about 87-100 % of peak effects.

The decrease in blood pressure occurs rapidly. In responding patients, normalisation is achieved within a month and persists without the occurrence of tachyphylaxis.

Discontinuation of treatment does not lead to a rebound effect. Perindopril reduces left ventricular hypertrophy.

In man, perindopril has been confirmed to demonstrate vasodilatory properties. It improves large artery elasticity and decreases the media-lumen ratio of small arteries.

 

An adjunctive therapy with a thiazide diuretic produces an additive-type of synergy. The combination of an ACE inhibitor and a thiazide also decreases the risk of hypokalaemia induced by the diuretic treatment.

 

Patients with stable coronary artery disease:

 

The EUROPA study was a multicentre, international, randomised, double-blind, placebo-controlled clinical trial lasting 4 years.

 

Twelve thousand two hundred and eighteen (12218) patients aged over 18 were randomised to 8 mg perindopril tert-butylamine (n=6110) or placebo (n=6108).

 

The trial population had evidence of coronary artery disease with no evidence of clinical signs of heart failure. Overall, 90% of the patients had a previous myocardial infarction and/or a previous coronary revascularisation. Most of the patients received the study medication on top of conventional therapy including platelet inhibitors, lipid lowering agents and beta-blockers.

 

The main efficacy criterion was the composite of cardiovascular mortality, non fatal myocardial infarction and/or cardiac arrest with successful resuscitation. The treatment with 8 mg perindopril tertbutylamine once daily resulted in a significant absolute reduction in the primary endpoint of 1.9% (relative risk reduction of 20%, 95%CI [9.4; 28.6] – p<0.001).

 

In patients with a history of myocardial infarction and/or revascularisation, an absolute reduction of 2.2% corresponding to a RRR of 22.4% (95%CI [12.0; 31.6] – p<0.001) in the primary endpoint was observed by comparison to placebo.

 

Paediatric population:

 

The safety and efficacy of perindopril in children and adolescents aged below 18 years have not been established (see section 4.2).

In an open, non-comparative clinical study in 62 hypertensive children aged from 2 to 15 years with a glomerular filtration rate >30 ml/min/1.73 m2, patients received perindopril with an average dose of

0.07 mg/kg. The dose was individualised according to the patient profile and blood pressure response up to a maximum dose of 0.135 mg/kg/day.

59 patients completed the period of three months, and 36 patients completed the extension period of the study, i.e. were followed at least 24 months (mean study duration: 44 months).

Systolic and diastolic blood pressure remained stable from the inclusion to the last assessment in patients previously treated by other antihypertensive treatments, and decreased in naïve patients. More than 75% of children had systolic and diastolic blood pressure below the 95th percentile at their last assessment.

The  safety  was  consistent  with   the   known   safety   profile   of   perindopril. Dual blockade of the renin-angiotensin-aldosterone system (RAAS) clinical trial data:

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 the 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.”

 

Linked to amlodipine:

 

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:

 

-              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.

 

-              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 1mm 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-center, 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 angiotensin-converting enzyme (ACE) inhibitors has shown that amlodipine did not lead to an increase in risk of mortality or combined mortality and morbidity in patients 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 of underlying ischaemic disease, on stable doses of ACE inhibitors, digitalis, and diuretics, amlodipine had no effect on total or 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).

 

Paediatric population

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 has also not been established. See section 4.2.

 


The rate and extent of absorption of perindopril and amlodipine from Vidonorm are not significantly different, respectively, from the rate and extent of absorption of perindopril and amlodipine from individual tablet formulations.

 

Linked to perindopril:

 

Absorption

After oral administration, the absorption of perindopril is rapid and the peak concentration is achieved within 1 hour. The plasma halflife of perindopril is equal to 1 hour.

 

Perindopril is a prodrug. Twenty seven percent of the administered perindopril dose reaches the bloodstream as the active metabolite perindoprilat. In addition to active perindoprilat, perindopril yields five metabolites, all inactive. The peak plasma concentration of perindoprilat is achieved within 3 to 4 hours.

 

As ingestion of food decreases conversion to perindoprilat, hence bioavailability, perindopril tert- butylamine should be administered orally in a single daily dose in the morning before a meal.

It has been demonstrated a linear relationship between the dose of perindopril and its plasma exposure. Distribution

The volume of distribution is approximately 0.2 l/kg for unbound perindoprilat. Protein binding of perindoprilat to plasma proteins is 20%, principally to angiotensin converting enzyme, but is concentration-dependent.

 

Elimination

Perindoprilat is eliminated in the urine and the terminal half-life of the unbound fraction is approximately 17 hours, resulting in steady-state within 4 days.

 

Special population

Elimination of perindoprilat is decreased in the elderly, and also in patients with heart or renal failure (see section 4.2). Dosage adjustment in renal insufficiency is desirable depending on the degree of impairment (creatinine clearance).

 

Dialysis clearance of perindoprilat is equal to 70 ml/min.

 

Perindopril kinetics are modified in patients with cirrhosis: hepatic clearance of the parent molecule is reduced by half. However, the quantity of perindoprilat formed is not reduced and therefore no dosage adjustment is required (see sections 4.2 and 4.4).

 

Linked to amlodipine:

 

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

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

The time to reach peak plasma concentrations of amlodipine is similar in older and younger subjects. Amlodipine clearance tends to be decreased with resulting increases in AUC and elimination half-life

 

in older 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. See section 4.2.

 


Linked to perindopril:

 

In the chronic oral toxicity studies (rats and monkeys), the target organ is the kidney, with reversible damage.

 

No mutagenicity has been observed in in vitro or in vivo studies.

 

Reproduction toxicology studies (rats, mice, rabbits and monkeys) showed no sign of embryotoxicity or teratogenicity. However, angiotensin converting enzyme inhibitors, as a class, have been shown to induce adverse effects on late fetal development, resulting in fetal death and congenital effects in rodents and rabbits: renal lesions and an increase in peri- and postnatal mortality have been observed. Fertility was not impaired either in male or in female rats.

No carcinogenicity has been observed in long term studies in rats and mice.

 

Linked to amlodipine:

 

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 the chromosome levels.

 

*Based on patient weight of 50 kg


Cellulose, microcrystalline, Polacrilin potassium,

Silica, hydrophobic colloidal, Magnesium stearate.


Not applicable.

 


3 years

This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from light and moisture.

 


30 tablets are in PA/Aluminium/PVC // Aluminium blister and carton box

 


No special requirements.

 

Any unused medicinal product or waste material should be disposed of in accordance with local requirements


Marketing Authorization Holder: AJA Pharmaceutical Industries Company, Ltd. Hail, 55414 Saudi Arabia Manufacturer : GEDEON RICHTER POLSKA Sp. z o.o.

June/2018
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