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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)

Coversyl is an angiotensin converting enzyme (ACE) inhibitor. These work by widening the blood vessels, which makes it easier for your heart to pump blood through them.

 

Coversyl is used:

-        to treat high blood pressure (hypertension),

-        to reduce the risk of cardiac events, such as heart attack, in patients with stable coronary artery disease (a condition where the blood supply to the heart is reduced or blocked) and who have already had a heart attack and/or an operation to improve the blood supply to the heart by widening the vessels that supply it.

 


a. Do not take Coversyl

-        if you are allergic to perindopril or any of the other ingredients of this medicine (listed in Section 6), or to any other ACE inhibitor.

-        if you have experienced symptoms such as wheezing, swelling of the face, tongue or throat, 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 are more than 3 months pregnant (It is also better to avoid Coversyl in early pregnancy – see pregnancy and breast-feeding section).

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

-        if you are having dialysis or any other type of blood filtration. Depending on the machine that is used, Coversyl may not be suitable for you.

-        if you have kidney problems where the blood supply to your kidneys is reduced (renal artery stenosis).

-        if you have taken or are currently taking with sacubitril/valsartan, a medicine for heart failure, as the risk of angioedema (rapid swelling under the skin in an area such as the throat) is increased (see “Warning and Precaution” and “Other medicines and Coversyl”).

 

b. Take special care with Coversyl

If any of the following apply to you please talk to your doctor, pharmacist or nurse before taking Coversyl:

 if you:

-        have aortic stenosis (narrowing of the main blood vessel leading from the heart) or hypertrophic cardiomyopathy (heart muscle disease) or renal artery stenosis (narrowing of the artery supplying the kidney with blood),

-        have any other heart problems,

-        have liver problems,

-        have kidney problems or if you are receiving dialysis,

-        have abnormally increased levels of a hormone called aldosterone in your blood (primary aldosteronism),

-        suffer from a collagen vascular disease (disease of the connective tissue) such as systemic lupus erythematosus or scleroderma,

-        have diabetes,

-        are on a salt restricted diet or use salt substitutes which contain potassium,

-        are to undergo anaesthesia and/or major surgery,

-        are to undergo LDL apheresis (which is 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,

-        have recently suffered from diarrhoea or vomiting, or are dehydrated,

-        have been told by your doctor or health care provider that you have an intolerance to some sugars,

-        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 or health care provider may check your kidney function, blood pressure, and the amount of electrolytes (e.g. potassium) in your blood at regular intervals.

See also information under the heading “Do not take Coversyl”.

-        are of black origin since you may have a higher risk of angioedema and this medicine may be less effective in lowering your blood pressure than in non-black patients.

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

-         racecadotril (used to treat diarrhea)

-         sirolimus, everolimus, temsirolimus and other drugs belonging to the class of so-called mTor inhibitors (used to avoid rejection of transplanted organs and for cancer),

-        sacubitril (available as fixed-dose combination with valsartan), used to treat long-term heart failure.

-        linagliptin, saxagliptin, sitagliptin, vildagliptin and other drugs belonging to the class of the also called gliptins (used to treat diabetes).

 

Angioedema

Angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat with difficulty in swallowing or breathing) has been reported in patients treated with ACE inhibitors, including Coversyl. This may occur at any time during treatment. If you develop such symptoms, you should stop taking Coversyl and see a doctor or health care provider immediately. See also section 4.

 

You must tell your doctor or health care provider if you think you are (or might become) pregnant. Coversyl 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 pregnancy and breast-feeding section).

 

Patients with rare hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the Lapp lactase deficiency should not take this medicinal product.

 

Children and adolescent

The use of perindopril in children and adolescents up to the age of 18 years is not recommended.

 

c. Taking other medicines, herbal or dietary supplements and Coversyl

Please tell your doctor, health care provider or pharmacist if you are taking, or have recently taken or might take any other medicines.

Treatment with Coversyl can be affected by other medicines. Your doctor or health care provider may need to change your dose and/or to take other precautions. These include:

-        other medicines for high blood pressure, including angiotensin II receptor blocker (ARB), aliskiren (see also information under the headings “Do not take Coversyl” and “Take special care with Coversyl”), or diuretics (medicines which increase the amount of urine produced by the kidneys),

-        potassium-sparing  drugs (e.g. triamterene, amiloride), potassium supplements or potassium-containing salt substitutes, other drugs which can increase potassium in your body (such as heparin, a medicine used to thin blood to prevent clots; trimethoprim and co-trimoxazole also known as trimethoprim/sulfamethoxazole for infections caused by bacteria),

-        potassium-sparing  drugs used in the treatment of heart failure : eplerenone and spironolactone at doses between 12,5 mg to 50 mg by day,

-        lithium for mania or depression,

-        non-steroidal anti-inflammatory drugs (e.g. ibuprofen) for pain relief or high dose acetylsalicylic acid, a substance presents in many medicines used to relieve pain and lower fever, as well as to prevent blood clotting,

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

-        baclofen (used to treat muscle stiffness in diseases such as multiple sclerosis),

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

-        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),

-        trimethoprim (for the treatment of infections),

-        estramustine (used in cancer therapy),

-        sacubitril/valsartan (used to treat long-term heart failure). See sections “Do not take Coversyl” and “Warnings and precautions”.

-        allopurinol (for the treatment of gout),

-        procainamide (for the treatment of an irregular heart beat),

-        vasodilators including nitrates (products that make the blood vessels become wider),

-        medicines used for the treatment of low blood pressure, shock or asthma (e.g. ephedrine, noradrenaline or adrenaline),

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

 

d. Taking Coversyl with food and drink

It is preferable to take Coversyl before a meal.

 

e. Pregnancy and breast-feeding

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

 

Pregnancy

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

 

Breastfeeding

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

 

f. Driving and using machines

Coversyl usually does not affect alertness but dizziness or tiredness  due to low blood pressure may occur in certain patients. If you are affected in this way, your ability to drive or to operate machinery may be impaired.

 

g. Important information about some of the ingredients of Coversyl

Coversyl contains lactose monohydrate. If you have been told by your doctor or health care provider that you have an intolerance to some sugars, contact your doctor or health care provider before taking this medicinal product. Coversyl contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

 


Always take this medicine exactly as your doctor has told you. Check with your doctor, health care provider 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 or health care provider will decide on the correct dose for you.

 

The recommended dosages are as follows:

High blood pressure: the usual starting and maintenance dose is 5 mg once daily. After one month, this can be increased to 10 mg once a day if required. 10 mg a day is the maximum recommended dose for high blood pressure.

If you are 65 or older, the usual starting dose is 2.5 mg once a day. After a month this can be increased to 5 mg once a day and then if necessary to 10 mg once daily.

Stable coronary artery disease: the usual starting dose is 5 mg once daily. After two weeks, this can be increased to 10 mg once daily, which is the maximum recommended dose in this indication.

If you are 65 or older, the usual starting dose is 2.5 mg once a day. After a week this can be increased to 5 mg once a day and after a further week to 10 mg once daily.

 

Use in children and adolescent

Use in children and adolescent is not recommended.

 

a. If you take more Coversyl than you should

Contact your doctor,  your pharmacist or the nearest hospital immediately. The most likely effect in case of overdose is low blood pressure which can lead to vertigo or dizziness . If this happens, lying down with the legs raised can help.

 

b. If you forget to take Coversyl

It is important to take your medicine every day as regular treatment works better. However, if you forget to take a dose of Coversyl 10 mg film-coated tablets, take the next dose at the usual time.  Do not take a double dose to make up for a forgotten dose.

 

c. If you stop taking Coversyl

As the treatment with Coversyl is usually life-long, you should discuss with your doctor or health care provider before stopping this medicinal product.

 

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

 


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

 

Stop taking the medicinal product and see a doctor or health care provider immediately, if you experience any of the following side effects that can be serious:

-          swelling of the face, lips, mouth, tongue or throat, difficulty in breathing (angioedema) (See section 2.b) “Take special care with Coversyl”) (Uncommon may affect up to 1 in 100 people),

-          severe dizziness or fainting due to low blood pressure (Common - may affect up to 1 in 10 people,

-         unusual fast or irregular heartbeat, chest pain (angina) or heart attack (Very rare - may affect up to 1 in 10,000 people),

-         weakness of arms or legs, or problems speaking which could be a sign of a possible stroke (Very rare – may affect up to 1 in 10,000 people),

-         sudden wheeziness, chest pain, shortness of breath, or difficulty in breathing (bronchospasm) (Uncommon - may affect up to 1 in 100 people),

-         inflamed pancreas which may cause severe abdominal and back pain accompanied with feeling very unwell (Very rare - may affect up to 1 in 10,000 people),

-         yellowing of the skin or eyes (jaundice) which could be a sign of hepatitis (Very rare - may affect up to 1 in 10,000 people),

-         skin rash which often starts with red itchy patches on your face, arms or legs (erythema multiforme) (Very rare - may affect up to 1 in 10,000 people).

 

Tell your doctor or health care provider if you notice any of the following side effects:

Common (may affect up to 1 in 10 people):

-                 headache,

-                 dizziness,

-                 vertigo,

-                 pins and needles,

-                 vision disturbances,

-                 tinnitus (sensation of noises in the ears),

-                 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,

-                 tiredness.

 

Uncommon (may affect to 1 in 100 people):

-                depression,

-                mood swings,

-                sleep disturbances,

-                dry mouth,

-                 intense itching or severe skin rashes,

-                formation of blister clusters over the skin,

-                kidney problems,

-                impotence,

-                sweating,

-                excess of eosinophils (a type of white blood cells),

-                somnolence,

-                fainting,

-                palpitations,

-                tachycardia,

-                vasculitis (inflammation of blood vessels),

-                photosensitivity reaction (increased sensitivity of the skin to sun),

-                arthralgia (joint pain),

-                myalgia (muscle pain),

-                chest pain,

-                malaise,

-                oedema peripheral,

-                fever,

-                fall,

-                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.

 

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

-                acute renal failure,

-                dark urine, feeling sick (nausea) or being sick (vomiting), muscle cramps, confusion and seizures.     These may be symptoms of a condition called SIADH (inappropriate antidiuretic hormone secretion).

-                decreased or absent urine output,

-                flushing, 

-                changes in laboratory parameters: Increased level of liver enzymes, high level of serum bilirubin.

 

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

-                confusion,

-                eosinophilic pneumonia (a rare type of pneumonia),

-                rhinitis (blocked up or runny nose),

-                 

-                changes in blood values such as a lower number of white and red blood cells, lower haemoglobin, lower number of blood platelets.

 

If you have these symptoms contact your doctor as soon as possible.

 

 

Unknown frequency (cannot be estimated from the available data

•           discolouration, numbness and pain in fingers or toes (Raynaud’s phenomenon).

 

Reporting of side effects

If you get any side effects, talk to your doctor, health care provider or pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the national reporting system. By reporting side effects you can help provide more information on the safety of this medicine.

 


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

Store below 30°C. Keep the tablet container tightly closed in order to protect from moisture.

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

 

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


-              The active substance is perindopril arginine. One film-coated tablet contains 6.790 mg perindopril (corresponding to 10 mg perindopril arginine).

-              The other ingredients in the tablet core are: lactose monohydrate, magnesium stearate, maltodextrin, hydrophobic colloidal silica, sodium starch glycolate (type A), and in the tablet film-coating: glycerol, hypromellose, copper chlorophyllin, macrogol 6000, magnesium stearate, titanium dioxide.


Coversyl 10 mg tablets are green, round, biconvex, film-coated tablets engraved with on one face and on the other face. The tablets are available in box of 30 tablets. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Les Laboratoires Servier

50 rue Carnot

92284 Suresnes cedex – France

 

Manufacturer

Servier (Ireland) Industries Ltd

Gorey Road

Arklow - Co. Wicklow – Ireland

 

Packed by

AJA Pharmaceutical Industries Company Ltd

Building No. 6979, Hail Industrial City, Hail 55414

Saudi Arabia

Tel.: +966 11 268 7900

Fax: +966 11 268 7911

 

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

 

Saudi Arabia  

Servier Saudi Arabia Scientific Office  

3533 As Sulaimaniyah - Hitteen Dist.  

1st floor - Office #101  

Kingdom of Saudi Arabia 

Tel.: +966 011 252 2330 

E-mail: regulatory.sa1@servier.com  

Gulf Countries  

Les Laboratoires Servier Scientific Office  

P.O. Box 1586, Level 15, Arenco Tower, Dubai Media city, Sheikh Zayed Road,  

Dubai, UAE  

Tel: +971 4 3329903  

E-mail: magdy.abdou@servier.com  

 


This leaflet was last revised in 11.2021. e. To report any side effect(s): • Saudi Arabia: - National Pharmacovigilance Center (NPC) - SFDA call Center 19999 - E-mail: npc.drug@sfda.gov.sa - Website: https://ade.sfda.gov.sa/ • Other GCC states: - Please contact the relevant competent authority. f. Council of Arab Health Ministers: This is a Medicament - Medicament is a product which affects your health and its consumption contrary to instructions is dangerous for you. - Follow the doctor's prescription, the method of use and the instruction of the pharmacist who sold the medicament. - The doctor and the pharmacist are the experts in medicines, their benefits and risks. - Do not by yourselves interrupt the period of treatment prescribed for you. - Do not repeat the same prescription without consulting your doctor. - Keep all medicaments out of reach of children Council of Arab Health Ministers Union of Arab Pharmacists g. This patient information leaflet is approved by the Saudi Food and Drug Authority
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

التصنيف الدوائي العلاجي: مثبط لإنزيم التحويل غير المرتبط.

رمز التصنيف التشريحي العلاجي: C09AA04

إن كوفرسيل هو عبارة عن مثبط لخميرة تحويل الأنجيوتنسين (ACE inhibitor)، وهو يقوم بتوسيع الأوعية الدموية مسهلاً بذلك عمل القلب بضخ الدم عبرها.

 

يستعمل كوفرسيل في الحالات التالية:

-        في علاج ارتفاع الضغط الشرياني.

-    لتخفيض خطر التعرّض للحوادث القلبية، مثل السكتة القلبية، لدى المصابين بمرض الشريان التاجي الثابت (أي أن جريان الدم الوارد للقلب  ضئيل أو محصور) ولدى من أصيبوا من قبل بسكتة قلبية، و/أو لدى من خضعوا لعملية تحسين ورود الدم للقلب عن طريق توسيع الشرايين التي تمد القلب بالدم.

 

أ. لا تتناول كوفرسيل في الحالات التالية:

-        إن كانت لديك حساسية (فرط الحساسية) من البيريندوبريل، أو من أي من مكونات كوفرسيل الأخرى (المذكورة في القسم ٦)، أو من الأدوية الأخرى التابعة لصنف مثبطات خميرة تحويل الأنجيوتنسين.

-        إن كنت تعرضت وقت علاج سابق بواسطة مثبطات خميرة تحويل الأنجيوتنسين لأعراض مثل صفير أثناء التنفس، أو تورم في الوجه أو في اللسان أو في الحنجرة، أو حكّة شديدة، أو حالات طفح جلدي شديد، أو إن سبق وظهرت تلك الأعراض في أي ظروف أخرى لك أو لأحد أفراد عائلتك (وهي حالة يُطلق عليها وذمة وعائيّة).

-        في حال كنتِ حاملًا منذ أكثر من ثلاثة أشهر (كما يستحسن عدم أخذ كوفرسيل منذ بداية الحمل – أنظري إلى مقطع الحمل والإرضاع ).

-        إذا كنت مصابا بالسكّري أو باضطراب الوظيفة الكلوية وتتلقى علاجا خافضا لضغط الدم يحتوي على أليسكيرين.

-        إذا كنت تخضع لعملية الديلزة أو أي نوع آخر من عمليات تنقية الدم. حسب الدواء المستعمل، قد لا يكون كوفرسيل مناسبا لك،

-        إذا كنت تعاني من مشاكل كلوية حيث تقل التروية الدموية لكليتيك (تضيق الشريان الكلوي).

-        إذا كنت قد تلقيت أو تتلقى حاليا علاجا بـ ساكوبتريل/فالسارتان، وهو دواء لعلاج قصور القلب نظرا لاردياد إمكانية حدوث الوذمة الوعائية (تورم سريع تحت الجلد في منطقة كالبلعوم) (راجع قسمي "تحذيرات واحتياطات" و "الأدوية الأخرى كوفيرسيل")،

 

 

 

ب. يجب توجيه عناية خاصة أثناء تناول كوفرسيل

إن كنت تشكو من إحدى الحالات التالية فالرجاء التحدث إلى طبيبك ,الصيدلاني أو الممرضة قبل تناول كوفرسيل:

 

-        إن كنت :

-         تعاني من تضيّق أبهري (أي تضيّق في الشريان الرئيسي الذي يخرج من القلب)، أو اعتلال مضخّم في عضلة القلب (أي مرض  في عضلة القلب)، أو تضيّق في الشريان الكلوي (أي تضيق في الشريان الذي يمد الكلية بالدم)،

-        تشكو من أي مشكلة قلبية أخرى،

-        تشكو من مشاكل في الكبد،

-        تشكو من مشاكل كلوية أو إن كنت خاضعا لتحال الدم،

-        إذا كنت تعاني من معدلات مرتفعة بشكل غير طبيعي من هرمون يدعى ألدوستيرون في دمك (فرط الألدوستيرونية الأولي)،

-        تشكو من داء وعائي كولاجيني (وهو عبارة عن مرض في النسيج الضامّ)، مثل الذئبة الحمامية الجهازية  أوالتصلّب الجلدي،

-        مصاباً بداء السكري،

-        خاضعاً لحمية منخفضة الملح أوتستعمل بدائل الملح التي تحتوي على البوتاسيوم،

-        سوف تخضع لتخدير طبّي و/أو كنت سوف تقوم بعمليّة جراحيّة هامة،

-        سوف تقوم بالسحب الآلي للبروتين الشحمي المنخفض الكثافة (LDL) (أي عمليّة آليّة لسحب الكوليسترول من الدم)،

-        سوف تقوم بعلاج لمكافحة التحسّس لتخفيف تأثير لدغات النحل والدبابير،

-        إن كنت قد شكوت مؤخّراً من الإسهال أو من القيء، أو إن كنت تعاني من الجفاف،

-        إأعلمك طبيبك أو مزوّد الرعاية الصحية بأنك لا تتحمّل بعض أنواع السكريات،

-        تتناول أيا من الأدوية التالية التي jستعمل لعلاج ضغط الدم المرتفع:

-        - حاصرات مستقبلات الأنجيوتنسين ΙΙ (التي تعرف أيضا باسم مجموعة السارتان – مثل فالسارتان، تلميسارتان، إربيسارتان)، وخاصة

-        إذا كنت تشكو من اضطرابات كلوية ذات صلة بالسكري.

- أليسكيرين.

 قد يقوم طبيبك أو مزوّد الرعاية الصحية بالتأكد من وظيفتك الكلوية، ضغط الدم، وكمية الشوارد الكهربائية (مثل البوتاسيوم) في دمك

على فترات منتظمة.

راجع أيضا المعلومات الواردة في قسم "لا تتناول كوفرسيل".

- تنتمي إلى العرق الأسود لأنك قد تكون أكثر عرضة لخطر الإصابة بالوذمة الوعائية وقد يكون هذا الدواء أقل فعالية في تخفيض ضغط دمك –

مقارنة بالمرضى من غير العرق الأسود.

-إن كنت تتناول أيا من الأدوية التالية، فإن إمكانية الأصابة بالوذمة الوعائية ترتفع:

-         راسيكادوتريل (الذي يستعمل لعلاج الإسهال)،

-         سيروليموس، إيفيروليموس، تمسيروليموس والأدوية الأخري التي تنتمي إلى مجموعة الأدوية التي تدعى مثبطات الهدف الميكانيكي لرابامايسين m-TOR inhibitors (التي تستعمل لتفادي رفض الأعضاء المزروعة ولعلاج السرطان)،

-            ساكوبتريل (الذي يوجد على شكل تركيبة ثابتة الجرعة مع فالسارتان)، الذي يستعمل لعلاج قصور القلب طويل الأمد.

-            ليناغلبتين، ساكساغلبتين، سيتاغلبتين، فيلداغلبتين، وكافة الأدوية الأخرى التي تنتمي إلى مجموعة غلبتين (التي تستعمل لعلاج السكري).

 

 

الوذمة الوعائية

تم الإبلاغ عن حدوث الوذمة الوعائية (تفاعل تحسسي شديد مع تورم في الوجه، الشفتين، اللسان أو الحلق مع صعوبة في البلع أوالتنفس) لدى المرضى الذين يعالجون بمثبطات خميرة تحويل الأنجيوتنسين، ومن ضمنها كوفرسيل. وقد تحدث في أي وقت أثناء العلاج. إذا أصبت بأعراض كهذه، فيجب أن تتوقف عن تناول كوفرسيل وتراجع طبيبا أو مزودا للرعاية الصحية على الفور. راجع أيضا القسم ٤.

 

عليكِ بإعلام طبيبك أو مزوّد الرعاية الصحية إن كنتِ تظنّين أنكِ حاملًا (أو إن كنتِ تتوقعين الحمل). فإنه لا يُنصح بأخذ كوفرسيل منذ بداية الحمل، ولا يجوز أخذه على الإطلاق بعد الشهر الثالث للحمل، حيث قد يسبب  إصابات خطيرة للطفل إذا تم تناوله في هذه المرحلة (أنظري إلى مقطع الحمل

 والإرضاع).

 

لا ينصح باستعمال هذا الدواء لدى المرضى الذين يعانون من عدم تحمل الجالاكتوز، ونقص اللاكتاز لاب أو من متلازمة سوء امتصاص الجلوكوز أو الجالاكتوز (أمراض وراثية نادرة).

 

 

الأطفال والمراهقون

لا ينصح باستعمال بريندوبريل للأطفال والمراهقين حتى عمر ١٨ سنة.

 

ج- تناول أو استعمال الأدوية الأخرى، أو المكملات العشبية أو الغذائية مع كوفرسيل

أعلم طبيبك أو مزوّد الرعاية الصحية أو الصيدلاني إذا كنت تتناول حالياً أو تناولت مؤخّراً أدوية أخرى.

 

إن العلاج بواسطة كوفرسيل قد يتأثر بالأدوية الأخرى قد يحتاج طبيبك أو مزوّد الرعاية الصحية إلى تغيير جرعتك و/أو اتخاذ احتياطات أخرى. وهذه تشمل:

-        الأدوية الأخرى المخفّضة للضغط الشرياني، بما فيها حاصرات مستقبلات الأنجيوتنسين ΙΙ، أليسكيرين (راجع أيضا المعلومات الواردة تحت عنوان "لا تتناول كوفرسيل" و"يجب توجيه عناية خاصة أثناء تناول كوفرسيل" ،مدرّات البول (أي الأدوية التي ترفع مقدار البول الناتج عن الكليتين)،

-        الأدوية الموفّرة للبوتاسيوم ( تريامتيرين، أميلوريد)، أو مكملات البوتاسيوم، أو بدائل الملح المحتوية على البوتاسيوم، أدوية أخرى يمكنها رفع معدلات البوتاسيوم في جسمك (مثل الهيبارين الذي يستعمل لتمييع الدم ومنع التخثر؛ وترايميثوبريم وكوتريموكسازول والمعروف أيضا باسم ترايميثوبريم/سلفاميثوكسازول لعلاج حالات العدوى البكترية)

-        الأدوية الموفّرة للبوتاسيوم والمستعملة في علاج قصور القلب: إيبليرينون وسبيرونولاكتون بجرعات تتراوح بين ١٢٫٥ ملغم و٥٠ ملغم يوميا،

-        الليثيوم المُستعمل في علاج الذهان الهَوَسي أو الاكتئاب،

-        الأدوية المضادة للالتهاب غير الستيرويديّة (مثل الإيبوبروفين) التي تستعمل لمكافحة الألم أو الجرعات المرتفعة من حمض الأستيل ساليسيليك، المادة التي توجد في العديد من الأدوية التي تستعمل لتخفيف الألم وخفض الحرارة، بالإضافة إلى منع تشكل الخثرات،

-        الأدوية المستعملة في علاج داء السكّري (مثل الأنسولين أو المتفورمين)،

-        باكلوفين (المستعمل في علاج التصلب العضلي في أمراض مثل التصلب المتعدد)،

-        الأدوية المستعملة في علاج الاضطرابات العقلية مثل الاكتئاب أو القلق أو الفصام إلخ (منها مضادات الاكتئاب ثلاثيّة الحلقات ومضادات الذهان)،

-        كابتات المناعة (أي الأدوية المخفّضة لآليّات المناعة في الجسم) المستعملة في علاج أمراض المناعة الذاتيّة أو بعد عمليّة غرس الأعضاء (منها سيكلوسبورين، تاكروليموس)،

-        ترايميثوبريم (لعلاج حالات العدوى)،

-        إسترامُستين (الذي يستعمل لعلاج السرطان)،

-        الأدوية، التي كثيرا ما تستعمل لعلاج الإسهال (راسيكادوتريل) أو تفادي رفض الأعضاء المزروعة (سيروليموس، إيفيروليموس، تيمسيروليموس وأدوية أخرى من الأدوية التي تدعى مثبطات m-Tor). راجع قسم "تحذيرات واحتياطات"،

-        ساكوبتريل / فالسارتان (الذي يستعمل لعلاج قصور القلب طويل الأمد). راجع قسمي "لا تتناول كوفرسيل" و "تحذيرات واحتياطات".

-        آلوبورينول (لعلاج النقرس)،

-        بروكايين آميد (لعلاج اضطرابات ضربات القلب)،

-        الموسّعات الوعائيّة بما فيها النترات (المستحضرات التي من شأنها توسيع الأوعية الدمويّة)،

-        الأدوية المستعملة في علاج هبوط الضغط الشرياني، أو في علاج الصدمة أو في علاج الربو (منها إيفيدرين أو نورادرينالين أو أدرينالين)،

-        أملاح الذهب، وخاصة التي تعطى داخل الوريد (والتي تستعمل لعلاج أعراض التهاب المفاصل الروماتويدي).

 

د. تناول كوفرسيل مع الطعام والشراب

من المستحسن أخذ كوفرسيل قبل وجبة الطعام.

 

 

يحتوي كوفرسيل 10 ملغ، حبّات ملبّسة على الصوديوم 

يحتوي كوفرسيل 10 ملغ على أقل من ١ ميليمول (٢٣ ملغ) من الصوديوم لكل جرعة، مما يعني أنه بالأساس "خال من الصوديوم".

 

 

هـ. الحمل والإرضاع

إذا كنت حاملا أو مرضعا، أو تعتقدين بأنك حامل أو تخططين للإنجاب، عليكِ باستشارة طبيبك أو مزوّد الرعاية الصحية أو الصيدلاني قبل المباشرة بأخذ هذا  الدواء.

 

الحمل

يجب أن تبلغي طبيبك أو مزوّد الرعاية الصحية إذا كنت تعتقدين بأنك حامل (أو أنك قد تصبحين حاملًا). سينصحك طبيبك أو مزوّد الرعاية الصحية في الأحوال الطبيعية بالتوقف عن تناول كوفرسيل قبل حدوث الحمل أو بمجرد أن تعلمي بحدوثه. وسوف ينصحك بتناول دواء آخر بدلا عن كوفرسيل. يوصى بعدم تناول كوفرسيل منذ بداية الحمل، ولا يجوز أخذه على الإطلاق بعد الشهر الثالث للحمل، فقد يؤدي هذا إلى إصابات خطيرة للطفل.

.

 

الإرضاع

أبلغي طبيبك أو مزوّد الرعاية الصحية إن كنت مرضعا أو إن كنت سوف تباشرين بالإرضاع. لا يُنصح بأخذ كوفرسيل لدى المرأة المرضع. فإن كنت مصرّة على الإرضاع، بإمكان طبيبك أو مزوّد الرعاية الصحية أن يختار لك دواء آخر، وخاصة إن كان الطفل حديث الولادة أو خديجا (مولودا قبل الأوان).

 

و. قيادة السيارات وتشغيل الآليات

رغم أن كوفرسيل لا يؤثّر على اليقظة، بيد أنه قد يظهر إحساس بالدوار أو بالتعب لدى بعض المرضى  نتيجة هبوط ضغط الدم. إذا حدث لك هذا فقد تقل قدرتك على قيادة السيارات أو تشغيل الآلات.

 

 

ز. معلومات مهمة تتعلق ببعض مكونات كوفرسيل

يحتوي كوفرسيل على سكر الحليب (لاكتوز) أحادي الهيدرات. فإن سبق وأعلمك طبيبك أو مزوّد الرعاية الصحية بعدم تحمّلك لبعض أنواع السكريات، فعليك باستشارة طبيبك أو مزوّد الرعاية الصحية قبل أخذ هذا الدواء.

                                   

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عليك دائماً بالتقيّد بالجرعة التي وصفها لك طبيبك. فإن شككت بالأمر، عليك باستشارة طبيبك أو مزوّد الرعاية الصحية أو الصيدلاني.

يجب ابتلاع القرص مع كأس من الماء، ويُستحسن أخذه يوميّاً في نفس التوقيت في الصباح قبل وجبة الإفطار. إن طبيبك أو مزوّد الرعاية الصحية هو الذي يحدّد مقدار الجرعة المناسبة لوضعك.

 

يبلغ مقدار الجرعة الموصى بها كالتالي:

 

ارتفاع الضغط الشرياني: إن الجرعة المعتادة في بداية العلاج وجرعة المداومةعبارة عن ٥ ملغ تؤخذ مرّة واحدة في اليوم. وإن تطلّب الأمر، يمكن رفع هذه الجرعة، بعد شهر من العلاج، إلى ١٠ ملغ تؤخذ مرّة واحدة في اليوم. ١٠ ملغ هي الجرعة القصوى الموصى بها لعلاج ارتفاع الضغط الشرياني.

فإن بلغت أو تجاوزت ٦٥ سنة من العمر، تكون الجرعة المعتادة في بداية العلاج عبارة عن ٢٫٥ ملغ تؤخذ مرّة واحدة في اليوم، يمكن رفعها، بعد شهر من العلاج، إلى ٥ ملغ، ثم إلى ١٠ ملغ تؤخذ مرّة واحدة في اليوم إن تطلّب الأمر.

 

مرض الشريان التاجي  الثابت: الجرعة المعتادة في بداية العلاج عبارة عن ٥ ملغ تؤخذ مرّة واحدة في اليوم، يمكن رفعها، بعد أسبوعين من العلاج، إلى ١٠ ملغ تؤخذ مرّة واحدة في اليوم وهي الجرعة القصوى الموصى بها في هذه الحالة.

إن بلغت أو تجاوزت ٦٥ سنة من العمر، تكون الجرعة المعتادة في بداية العلاج عبارة عن ٢٫٥ ملغ تؤخذ مرّة واحدة في اليوم، يمكن رفعها، بعد أسبوع من العلاج، إلى ٥ ملغ ، ثم إلى ١٠ ملغ تؤخذ مرّة واحدة في اليوم الأسبوع التالي.

 

الاستعمال لدى الأطفال والمراهقين

لا يوصى بإعطاء كوفرسيل للأطفال والمراهقين.

 

أ-  إذا تناولت جرعة أكبر مما ينبغي من كوفرسيل

اتّصل بطبيبك, الصيدلاني أو أقرب مستشفى فوراً. فأكثر ما يُحتمل وقوعه في حال الإفراط بالجرعة، هو هبوط الضغط الشرياني، الذي قد يسبب الدوار أو الإغماء. فإن حصل لك هذا، فقد يساعدك الاستلقاء مع رفع ساقيك للأعلى.

 

ب. إذا نسيت أن تتناول كوفرسيل

من المهم جدًا أن تتناول دواءك كل يوم لأن العلاج المنتظم أكثر فعالية.  ولكن إذا نسيت تناول جرعة من كوفرسيل ١٠ ملغ، حبّات ملبّسة، عليك أن تتناول الجرعة التالية في التوقيت المعتاد. لا تتناول جرعة مضاعفة للتعويض عن الجرعة التي نسيت تناولها.

                                                  

ج. إذا توقفت عن تناول كوفرسيل

نظرا لأن العلاج بواسطة كوفرسيل عادةً ما يستمر مدى الحياة، لذا ينبغي عليك أن تستشير طبيبك أو مزوّد الرعاية الصحية قبل التوقّف عن تناول هذا المستحضر الدوائي.

فإن كانت لديك أي أسئلة إضافية بخصوص استعمال هذا الدواء، عليك باستشارة طبيبك أو مزوّد الرعاية الصحية أو الصيدلاني أو الممرضة.

 

كما هي الحال مع كافة الأدوية، من الممكن أن يسبب كوفرسيل آثارا جانبية ، رغم أنها لا تصيب كافة الأشخاص.

 

إن لاحظت حدوث أيّ من الآثار الجانبيّة التالية التي قد تكون خطيرة، عليك التوقف عن أخذ هذا الدواء والاتصال بطبيب أوبمزوّد للرعاية الصحية فوراً:

-        تورّم الوجه، أو الشفتين، أو الفم، أو اللسان، أو الحنجرة، صعوبة التنفّس  (وذمة وعائية) (راجع القسم ٢.ب "يجب توجيه عناية خاصة أثناء تناول كوفرسيل") (غير شائعة-  قد تصيب حتى ١ من بين ١٠٠ مستخدم)،

-        دوار شديد أو إغماء بسبب ضغط الدم المنخفض (شائع - قد يصيب حتى ١من بين ١٠ مستخدمين)،

-        تسرّع غير عادي أو عدم انتظام في ضربات القلب، ألم في الصدر (ذبحة صدرية) أو نوبة قلبية (نادرة جداً - قد تصيب حتى ١  من بين ١٠٠٠٠ مستخدم)،

-        ضعف في الذراعين أو الساقين، أو صعوبة في الكلام قد تكون علامة لسكتة دماغية محتملة (نادرة جداً - قد تصيب حتى ١  من بين ١٠٠٠٠ مستخدم)،

-        صفير مفاجئ في الصدر، ألم في الصدر، ضيق النفس، أو صعوبة التنفس (تشنج قصبي) (غير شائعة - قد تصيب حتى ١ من بين ١٠٠ مستخدم)،

-        التهاب البنكرياس الذي قد يسبب ألما شديدا في البطن والظهر مترافقا مع شعور بالتوعّك الشديد (نادر جداً - قد يصيب حتى١   من بين ١٠٠٠٠ مستخدم)،

-        اصفرار لون الجلد أو العينين (يرقان) الذي قد يكون علامة لالتهاب الكبد (نادر جداً - قد يصيب حتى١  من بين ١٠٠٠٠ مستخدم)،

-        طفح جلدي كثيرا ما يبدأ ببقع حاكّة على وجهك، ذراعيك أو ساقيك (حُمامى متعددة الأشكال) (نادرة جداً - قد تصيب حتى١  من بين ١٠٠٠٠ مستخدم).

 

أخبر طبيبك أو مزوّد الرعاية الصحية إذا لاحظت حدوث أيّ من الآثار الجانبيّة التالية:

-        الشائعة (أي تصيب حتى ١من بين ١٠ مستخدمين):

- صداع،

- دوخة،

- الإحساس بالدوار،

- الإحساس بوخز الإبر والدبابيس،

- اضطرابات بالنظر،

- الطنين (الإحساس بالضجيج في الأذن)، 

- سعال،

- ضيق النفس (عسرة التنفس)،

- اضطرابات معدية معوية (غثيان، قيء، ألم البطن، اضطراب في التذوّق، عسر هضم أو صعوبة الهضم، إسهال، إمساك)،

- تفاعلات تحسسيّة (مثل حالات الطفح الجلدي، الحكة)

- تشنجات عضلية،

- الإحساس بالتعب.

 

-           غير الشائعة (تصيب حتى ١ من بين ١٠٠ مستخدم):

- اكتئاب،

- تبدلات مزاجية،

- اضطرابات في النوم،

- تجفف في الفم،

- حكة شديدة أو طفح جلدي شديد،

- تشكل تجمعات نفاطية على الجلد،

- اضطرابات كلويّة،

- عجز جنسي،

- تعرّق،

- زيادة عدد اليوزينيات (نوع من كريات الدم البيضاء)،

- نعاس،

- إغماء،

- خفقان القلب،

- تسرع القلب،

- التهاب الأوعية الدموية،

- تفاعلات تحسسية ضوئية (زيادة تحسس الجلد تجاه الشمس)،

- ألم المفاصل،

- ألم عضلي،

- ألم في الصدر،

- توعّك،

- وذمة محيطية،

 - ارتفاع الحرارة،

- سقوط،

- تغير في المعايير المخبرية: ارتفاع معدّل البوتاسيوم في الدم القابل للتراجع بعد إيقاف الدواء، انخفاض معدّل الصوديوم، انخفاض شديد في معدّل سكر الدم لدى المرضى المصابين بالسكري، ارتفاع معدّل اليوريا في الدم، وارتفاع معدّل الكرياتينين في الدم.

 

النادرة (قد تصيب حتى ١ من بين ١٠٠٠ مستخدم):

- فشل كلوي حاد،

- بول داكن، شعور بالغثيان أو الإصابة به، تشنجات عضلية، ارتباك ونوبات.

هذه الأعراض قد تكون ناجمة عن إفراز غير مناسب من الهرمون المضاد للإدرار (متلازمة الإفراز غير المناسب من الهرمون المضاد للإدرار)

- نقص أو انعدام إنتاج البول،

- تبيغ واحمرار الوجه،

- تدهور حالة الصدفية،

- تغير في المعايير المخبرية: ارتفاع معدّل الخمائر الكبدية، ارتفاع معدّل بيليروبين المصل.

 

-          النادرة جداً (قد تصيب حتى ١ من بين ١٠٠٠٠ مستخدم):

- ارتباك،

- ذات الرئة اليوزينية (نوع نادر من ذات الرئة)،

- زكام (أي انسداد أو سيلان الأنف)، 

- فشل كلوي حاد،

- تبدّلات في قيم الدم مثل تناقص أعداد الكريات البيضاء والحمراء، انخفاض الهيموغلوبين، تناقص عدد الصفيحات الدموية،

 

إذا ظهرت لديك هذه الأعراض، اتصل بطبيبك بأقرب فرصة ممكنة.

 

ذات معدّل حدوث غير معروف (لا يمكن تقدير معدل الحدوث استنادا إلى المعطيات المتوفرة):

- تغير لون وتنميل وألم أصابع اليدين أو أصابع القدم (متلازمة رينو).

 

الإبلاغ عن الآثار الجانبية

إذا أصبت بأي آثار جانبية، تحدّث إلى طبيبك، أو مزوّد الرعاية الصحية، أو الصيدلاني أو الممرضة. هذا يشمل أي آثار جانبية ممكنة حتى ولو لم يرد ذكرها في هذه النشرة.

يمكنك أيضا الإبلاغ عن التأثيرات الجانبية مباشرة عن طريق نظام الإبلاغ الوطني. بإبلاغك عن الآثار الجانبية يمكنك المساعدة في توفير مزيد من المعلومات عن سلامة هذا الدواء.

لا تدع الدواء في متناول أيدي الأطفال أو تحت نظرهم.

يحفظ هذا الدواء في مكان لا تتجاوز حرارته ٣٠ درجة مئوية. أغلق الزجاجة بإحكام لحمايتها من الرطوبة.

 

لا تستعمل هذا الدواءبعد انقضاء تاريخ الصلاحية المبيّن على العلبة الكرتونية وعلى الزجاجة. يشير تاريخ انتهاء الصلاحية إلى آخر يوم من الشهر المشار إليه.

 

لا تتخلص من أي مواد دوائية في مياه المجاري العامة أو مع قمامة المنزل.  اسأل الصيدلاني عن طريقة التخلص من الأدوية التي لم تعد بحاجة إليها. هذه

الإجراءات تساعد على حماية البيئة.

-   المادة الفعّالة هي بيريندوبريل أرجنين. كل قرص ملبّس يحتوي على ٦٫٧٩٠ ملغ من البيريندوبريل (بما يعادل ١٠ ملغ من البيريندوبريل أرجينين).

 

-    المكونات الأخرى داخل الحبّة: لاكتوز أحادي الماء، ستيارات المغنيزيوم، مالتودكسترين، السيليكا الغروانيّة الكارهة للماء، غليكولات النشاء الصودي

     (نوع آ)، وفي غشاء التلبيس: غليسيرول، هيبروملّوز، كلوروفيللين النحاس، ماكروغول ٦٠٠٠، ستيارات المغنيزيوم، ثاني أكسيد التيتانيوم.

إن حبّات كوفرسيل ١٠ ملغ، هي حبّات ملبّسة  بطبقة رقيقة ذات لون أخضر، مستديرة ومحدّبة الوجهين، نُقش شكل على أحد وجهيها وشكل  على الوجه الآخر.

تتوفر الحبّات في علبة تحتوي على ٣٠ حبّة.

قد لا يتم تسويق كافة أحجام العبوات.

صاحب إجازة التسويق

Les Laboratoires Servier

50 rue Carnot

92284 Suresnes cedex – France

 

 

التصنيع:

سـرفييـه (إيرلندا) للتصنيع المحدودة

Servier (Ireland) Industries Ltd

Gorey Road

Arklow - Co. Wicklow – Ireland

 

تمت التعبئة بواسطة شركة أجا للصناعات الدوائية المحدودة

مبنى رقم 6979 ، المدينة الصناعية بحائل، حائل 55414

المملكة العربية السعودية

هاتف: 966112687900+

فاكس: 966112687911+

 

للحصول على أي معلومات تتعلق بهذا الدواء، الرجاء الاتصال بالوكيل المحلي للجهة الحاملة لإجازة التسويق.

 

المملكة العربية السعودية 

المكتب العلمي لشركة سيرفير العربية السعودية  

3533 السليمانية ، حي حطين، مكتب 101 

المملكة العربية السعودية 

هاتف: ٩٦٦١١2522330+ 

البريد الالكتروني: regulatory.sa1@servier.com 

بلدان الخليج 

المكتب العلمي لمختبرات سيرفييه 

ص.ب. ١٥٨٦، الطابق 15، برج أرينكو، مدينة دبي الإعلامية 

طريق الشيخ زايد، دبي، الإمارات العربية المتحدة 

هاتف: ٩٧١٤٣٣٢٩٩٠٣+ 

البريد الالكتروني: magdy.abdou@servier.com

 

 

 

تمت المراجعة الأخيرة لهذه النشرة بتاريخ 11-2021 هـ. للإبلاغ عن التأثير(ات) الجانبية: • المملكة العربية السعودية - المركز الوطني للتيقظ الدوائي (NPC) - للاتصال بالرقم الموحد للهيئة العامة للغذاء والدواء 19999 - البريد الالكتروني: npc.drug@sfda.gov.sa - الموقع الالكتروني: https://ade.sfda.gov.sa/ • دول الخليج العربي الأخرى: - الرجاء الاتصال بالسلطات المختصة ذات الصلة. و. مجلس وزراء الصحة العرب: إن هذا لدواء - الدواء مستحضر يؤثر على صحّتك، واستهلاكه خلافاً للتعليمات يعرّضك للخطر. - تقيّد بوصفة الطبيب، وبطريقة الاستعمال المدوّنة، وبتعليمات الصيدلاني الذي صرف لك الدواء. - فالطبيب والصيدلاني هما الخبيران بالدواء ونفعه وضرره. - لا تقطع مدة العلاج الموصوفة لك من تلقاء نفسك. - لا تكرر استعمال نفس الدواء دون مراجعة الطبيب. - لا تدع الأدوية بمتناول أيدي الأطفال. مجلس وزراء الصحّة العرب وإتّحاد الصيادلة العرب هـ. هذه النشرة لمعلومات المريض حائزة على موافقة الهيئة العامة للغذاء والدواء في المملكة العربية السعودية
 Read this leaflet carefully before you start using this product as it contains important information for you

Coversyl 10 mg film-coated tablets

Perindopril arginine. One film-coated tablet contains 6.790 mg perindopril corresponding to 10 mg perindopril arginine. Excipient with known effect: 145.16 mg lactose monohydrate. For the full list of excipients, see section 6.1.

Film-coated tablet. Green, round, biconvex, film-coated tablet engraved with on one face and on the other face..

Hypertension

Treatment of hypertension.

 

Stable coronary artery disease

Reduction of risk of cardiac events in patients with a history of myocardial infarction and/or revascularisation.

 


Posology

The dose should be individualised according to the patient profile (see section 4.4) and blood pressure response.

 

Hypertension

Coversyl may be used in monotherapy or in combination with other classes of antihypertensive therapy (see sections 4.3, 4.4, 4.5 and 5.1).

The recommended starting dose is 5 mg given once daily in the morning.

Patients with a strongly activated renin-angiotensin-aldosterone system (in particular, renovascular hypertension, salt and/or volume depletion, cardiac decompensation or severe hypertension) may experience an excessive drop in blood pressure following the initial dose. A starting dose of 2.5 mg is recommended in such patients and the initiation of treatment should take place under medical supervision.

The dose may be increased to 10 mg once daily after one month of treatment.

Symptomatic hypotension may occur following initiation of therapy with Coversyl; this is more likely in patients who are being treated concurrently with diuretics. Caution is therefore recommended since these patients may be volume and/or salt depleted.

If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with Coversyl (see section 4.4).

In hypertensive patients in whom the diuretic cannot be discontinued, therapy with Coversyl should be initiated with a 2.5 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of Coversyl should be adjusted according to blood pressure response. If required, diuretic therapy may be resumed.

In elderly patients treatment should be initiated at a dose of 2.5 mg which may be progressively increased to 5 mg after one month then to 10 mg if necessary depending on renal function (see table below).

 

Stable coronary artery disease

Coversyl should be introduced at a dose of 5 mg once daily for two weeks, then increased to 10 mg once daily, depending on renal function and provided that the 5 mg dose is well tolerated.

Elderly patients should receive 2.5 mg once daily for one week, then 5 mg once daily the next week, before increasing the dose up to 10 mg once daily depending on renal function (see Table 1 “Dosage adjustment in renal impairment”). The dose should be increased only if the previous lower dose is well tolerated.

 

Special population

 

Patients with renal impairment

Dosage in patients with renal impairment should be based on creatinine clearance as outlined in table 1 below:

Table 1: dosage adjustment in renal impairment

Creatinine clearance (ml/min)

Recommended dose

ClCR ≥ 60

5 mg per day

30 < ClCR < 60

2.5 mg per day

15 < ClCR < 30

2.5 mg every other day

Haemodialysed patients *

ClCR < 15

2.5 mg on the day of dialysis

* Dialysis clearance of perindoprilat is 70 ml/min.

For patients on haemodialysis, the dose should be taken after dialysis.

 

Patients with hepatic impairment

No dosage adjustment is necessary in patients with hepatic impairment (see sections 4.4 and 5.2).

 

Paediatric population

The safety and efficacy of perindopril in children and adolescents aged below 18 years have not been established.

Currently available data are described in section 5.1 but no recommendation on a posology can be made.

Therefore, use in children and adolescents is not recommended.

 

Method of administration

For oral use.

Coversyl is recommended to be taken once daily in the morning before a meal.

 


• Hypersensitivity to the active substance, to any of the excipients listed in Section 6.1 or to any other ACE inhibitor; • 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 Coversyl with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR[Glomerular Filtration Rate] < 60 ml/min/1.73m²) (see sections 4.5 and 5.1). • Concomitant use with sacubitril/valsartan (see sections 4.4 and 4.5), • Extracorporeal treatments leading to contact of blood with negatively charged surfaces (see section 4.5), • Significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney (see section 4.4).

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

 

Aortic and mitral valve stenosis / hypertrophic cardiomyopathy

As with other ACE inhibitors, Coversyl 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 Coversyl 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 Coversyl 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 Coversyl 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 Coversyl in patients with a recent kidney transplantation.

 

Renovascular hypertension:

There is an increased risk of hypotension and renal insufficiency when patient with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with ACE inhibitors (see section 4.3). Treatment with diuretics may be a contributory factor. Loss of renal function may occur with only minor changes in serum creatinine even in patients with unilateral renal artery stenosis.

 

 

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 Coversyl (see section 4.8). This may occur at any time during therapy. In such cases, Coversyl 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.

 

The combination of perindopril with sacubitril/valsartan is contraindicated due to the increased risk of angioedema (see section 4.3). Sacubitril/valsartan must not be initiated until 36 hours after taking the last dose of perindopril therapy. If treatment with sacubitril/valsartan is stopped, perindopril therapy must not be initiated until 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5). Concomitant use of ACE inhibitors with NEP inhibitors (e.g. racecadotril), mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and gliptins (e.g. linagliptin, saxagliptin, sitagliptin, vildagliptin) may lead to an increased risk of angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment) (see section 4.5). Caution should be used when starting racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and gliptins (e.g. linagliptin, saxagliptin, sitagliptin, vildagliptin) in a patient already taking an ACE inhibitor.  

 

 

Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis

Rarely, patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulphate 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, Coversyl 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, ACE inhibitors can cause hyperkalaemia because they inhibit the release of aldosterone. The effect is usually not significant in patients with normal renal function. Risk factors for the development of hyperkalemia 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, co-trimoxazole also known as trimethoprim/sulfamethoxazole) and especially aldosterone antagonists or angiotensin-receptor blockers. 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. Hyperkalemia can cause serious, sometimes fatal arrhythmias. Potassium-sparing diuretics and angiotensin-receptor blockers should be used with caution in patients receiving ACE inhibitors, and serum potassium and renal function should be monitored. 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.

 

Primary aldosteronism

Patients with primary hyperaldosteronism generally will not respond to anti-hypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, the use of this product is not recommended.

 

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).

 

 

Excipients

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, glucose-galactose malabsorption, or total lactase deficiency should not take this medicinal product.

 

 

Level of sodium

Coversyl contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially ‘sodium-free’.

 


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).

 

 

Drugs increasing the risk of angioedema

Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated as this increases the risk of angioedema (see section 4.3 and 4.4). Sacubitril/valsartan must not be started until 36 hours after taking the last dose of perindopril therapy. Perindopril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.4).

Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and gliptins (e.g. linagliptin, saxagliptin, sitagliptin, vildagliptin) may lead to an increased risk for angioedema (see section 4.4).

 

Drugs inducing hyperkalaemia

Although serum potassium usually remains within normal limits, hyperkalaemia may occur in some patients treated with Coversyl 10 mg. Some drugs or therapeutic classes may increase the occurrence of hyperkalaemia: aliskiren, potassium salts, potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), ACE inhibitors, angiotensin-II receptors antagonists, NSAIDs, heparins, immunosuppressant agents such as ciclosporin or tacrolimus, trimethoprim and cotrimoxazole (trimethoprim/sulfamethoxazole), as trimethoprim is known to act as a potassium-sparing diuretic like amiloride. The combination of these drugs increases the risk of hyperkalaemia. Therefore, the combination of Coversyl 10 mg with the above-mentioned drugs is not recommended. If concomitant use is indicated, they should be used with caution and with frequent monitoring of serum potassium.

 

Concomitant use contra-indicated (see section 4.3)

Aliskiren

In diabetic or impaired renal patients, risk of hyperkalaemia, worsening of renal function and cardiovascular morbidity and mortality increase.

 

Extracorporeal treatments

Extracorporeal treatments leading to contact of blood with negatively charged surfaces such as dialysis or haemofiltration with certain high-flux membranes (e.g. polyacrylonitril membranes) and low density lipoprotein apheresis with dextran sulphate due to increased risk of severe anaphylactoid reactions (see section 4.3). If such treatment is required, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

 

 

Sacubitril/Valsartan

The concomitant use of perindopril with sacubitril/valsartan is contra-indicated as the concomitant inhibition of neprilysin and ACE may increase the risk of angioedema. Sacubitril/valsartan must not be started until 36 hours after taking the last dose of perindopril therapy. Perindopril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan (see section 4.3 and 4.4).

 

Concomitant use not recommended (see section 4.4)

Aliskiren

In patients other than diabetic or impaired renal patients, risk of hyperkalaemia, worsening of renal function and cardiovascular morbidity and mortality increase.

 

Concomitant therapy with ACE inhibitor and angiotensin-receptor blocker

It has been reported in the literature that in patients with established atherosclerotic disease, heart failure, or with diabetes with end organ damage, concomitant therapy with ACE inhibitor and angiotensin-receptor blocker is associated with a higher frequency of hypotension, syncope, hyperkalaemia, and worsening renal function (including acute renal failure) as compared to use of a single renin-angiotensin-aldosterone system agent. Dual blockade (e.g, by combining an ACE-inhibitor with an angiotensin II receptor antagonist) should be limited to individually defined cases with close monitoring of renal function, potassium levels, and blood pressure.

 

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 creatininemia 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 acetylsalicylic acid³ 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.

 

 

Tricyclic antidepressants/Antipsychotics/Anesthetics

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.


Pregnancy

 

The use of ACE inhibitors is not recommended during the first trimester of pregnancy (see section 4.4). The use of ACE inhibitors is contra-indicated during the 2nd and 3rd 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 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.

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 also sections 4.3 and 4.4).

 

Lactation

Because no information is available regarding the use of Coversyl 10 mg during breastfeeding, Coversyl 10 mg is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

 

Fertility

There was no effect on reproductive performance or fertility.

 


Coversyl has no direct influence on alertness but vertigo or fatigue related to low blood pressure may occur in some patients.

As a result the ability to drive or operate machinery may be impaired.


a.  Summary of safety profile

 

The safety profile of perindopril is consistent with the safety profile of ACE inhibitors:

The most frequent adverse events reported in clinical trials and observed with perindopril are: dizziness, headache, paraesthesia, vertigo, visual disturbances, tinnitus, hypotension, cough, dyspnoea, abdominal pain, constipation, diarrhoea, dysgeusia, dyspepsia, nausea, vomiting, prurit, rash, muscle cramps, and asthenia.

 

b. Tabulated list of adverse reactions

 

The following undesirable effects have been observed during clinical trials and/or post-marketing use with perindopril and ranked under the following frequency:

Very common (³1/10); common (³1/100, <1/10); uncommon (³1/1000, <1/100); rare (³1/10000, <1/1000); very rare (<1/10000); not known (cannot be estimated from the available data).

 

 

MedDRA

System Organ Class

Undesirable Effects

Frequency

Blood and the lymphatic System Disorders

Eosinophilia

Uncommon*

 

Agranulocytosis or pancytopenia

Very rare

 

Haemoglobin decreased and haematocrit decreased

Very rare

 

Leucopenia/neutropenia

Very rare

 

Haemolytic anaemia in patients with a congenital deficiency of G-6PDH (see section 4.4)

Very rare

 

Thrombocytopenia

Very rare

 

Endocrine disorders

Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Rare

 

Metabolism and Nutrition Disorders

Hypoglycaemia (see sections 4.4 and 4.5)

Uncommon*

 

Hyperkalaemia, reversible on discontinuation (see section 4.4)

Uncommon*

 

Hyponatraemia

Uncommon*

 

Psychiatric disorders

Depression

Uncommon*

 

Mood disturbances

Uncommon

 

Sleep disorder

Uncommon

 

Nervous System disorders

Dizziness

Common

 

Headache

Common

 

Paraesthesia

Common

 

Vertigo

Common

 

Somnolence

Uncommon*

 

Syncope

Uncommon*

 

Confusion

Very rare

 

Eye Disorders

Visual disturbances

Common

 

Ear and labyrinth disorders

Tinnitus

Common

 

Cardiac Disorders

Palpitations

Uncommon*

 

Tachycardia

Uncommon*

 

Angina pectoris (see section 4.4)

Very rare

 

Arrythmia

Very rare

 

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

Very rare

 

Vascular Disorders

Hypotension (and effects related to hypotension)

Common

 

Vasculitis

Uncommon*

 

Flushing

Rare*

 

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

Very rare

 

Raynaud’s phenomenon

Not known

 

Respiratory, Thoracic and Mediastinal Disorders

Cough 

Common

 

Dyspnoea

Common

 

Bronchospasm

Uncommon

 

Eosinophilic pneumonia

Very rare

 

Rhinitis 

Very rare

 

Gastro-intestinal Disorders

Abdominal pain

Common

 

Constipation

Common

 

Diarrhoea

Common

 

Dysgeusia

Common

 

Dyspepsia

Common

 

Nausea

Common

 

Vomiting

Common

 

Dry mouth

Uncommon

 

Pancreatitis

Very rare

 

Hepato-biliary Disorders

Hepatitis either cytolitic  or cholestatic (see section 4.4)

Very rare 

 

Skin and Subcutaneous Tissue Disorders

Prurit

Common

 

Rash

Common

 

Urticaria (see section 4.4)

Uncommon

 

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

Uncommon

 

Photosensitivity reactions

Uncommon*

 

Pemphigoid

Uncommon*

 

Hyperhydrosis

Uncommon

 

Erythema multiforme

Very rare

 

Musculoskeletal  And Connective Tissue Disorders

Muscle cramps

Common

 

Arthralgia

Uncommon*

 

Myalgia

Uncommon*

 

Renal and Urinary Disorders

Renal insufficiency

Uncommon

 

Acute renal failure

Rare

 

Anuria/Oliguria

Rare*

 

Reproductive System and Breast Disorders

Erectile dysfunction

Uncommon

 

General Disorders and Administration Site Condition

Asthenia

Common

 

Chest pain

Uncommon*

 

Malaise

Uncommon*

 

Oedema peripheral

Uncommon*

 

Pyrexia

Uncommon*

 

Investigations

Blood urea increased

Uncommon*

 

Blood creatinine increased

Uncommon*

 

Blood bilirubin increased

Rare

 

Hepatic enzyme increased

Rare

 

 

Injury, poisoning and procedural complications

Fall

Uncommon*

 

Clinical trials

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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

To report any side effect(s):

 

·   Saudi Arabia:

 

- National Pharmacovigilance Center (NPC)

          - Fax: +966-11-205-7662

          - SFDA call Center 19999

          - Toll free phone: 8002490000

          - E-mail: npc.drug@sfda.gov.sa

          - Website: www.sfda.gov.sa/npc

 

·   Other GCC states:

 

- Please contact the relevant competent authority.

 


Limited data are available for overdose in humans. Symptoms associated with 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. Perindopril may be removed from the general circulation by haemodialysis (see section 4.4). Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored continuously.


Mechanism of action

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 (equivalent to 10 mg perindopril arginine) (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 tert-butylamine (equivalent to 10 mg perindopril arginine) 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 use

The safety and efficacy of perindopril in children and adolescents aged below 18 years have not been established.

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 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.

 


Absorption

After oral administration, the absorption of perindopril is rapid and the peak concentration is achieved within 1 hour. The plasma half-life 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 arginine 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. 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).

 


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 foetal development, resulting in foetal 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.

 


Core:

Lactose monohydrate

Magnesium stearate

Maltodextrin

Hydrophobic colloidal silica

Sodium starch glycolate (type A)

 

Film-coating:

Glycerol

Hypromellose

Copper chlorophyllin

Macrogol 6000

Magnesium stearate

Titanium dioxide


Not applicable.


3 years.

Keep the bottle tightly closed in order to protect from moisture.

Store below 30°C.


White polypropylene tablet container equipped with a polyethylene flow reducer and a white opaque stopper containing a dessicant gel.

Box of 5, 10, 14, 20, 28, 30, 50, 60 (60 or 2 containers of 30), 84 (84 or 3 containers of 28), 90 (90 or 3 containers of 30), 100 (100 or 2 containers 50), 120 (120 or 4 containers of 30) or 500 tablets (500 or 10 containers of 50).

 

Not all pack sizes may be marketed.


No special requirements.


Les Laboratoires Servier - France

11-2021
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