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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)

Crestor belongs to a group of medicines called statins.

You have been prescribed Crestor because:

  • You have a high cholesterol level. This means you are at risk from a heart attack or stroke. Crestor is used in adults, adolescents and children 6 years or older to treat high cholesterol.

 

  • You have been advised to take a statin, because changing your diet and doing more exercise were not enough to correct your cholesterol levels. You should continue with your cholesterol-lowering diet and exercise while you are taking Crestor.
  •  

       Or

  • You have other factors that increase your risk of having a heart attack, stroke or related health problems.

Heart attack, stroke and other problems can be caused by a disease called atherosclerosis. Atherosclerosis is due to build-up of fatty deposits in your arteries.

Why it is important to keep taking Crestor

Crestor is used to correct the levels of fatty substances in the blood called lipids, the most common of which is cholesterol.

 

There are different types of cholesterol found in the blood – ‘bad’ cholesterol (LDL-C) and ‘good’ cholesterol (HDL-C).

 

  • Crestor can reduce the ‘bad’ cholesterol and increase the ‘good’ cholesterol.
  • It works by helping to block your body’s production of ‘bad’ cholesterol. It also improves your body’s ability to remove it from your blood.

 

For most people, high cholesterol does not affect the way they feel because it does not produce any symptoms. However, if it is left untreated, fatty deposits can build up in the walls of your blood vessels causing them to narrow.

Sometimes, these narrowed blood vessels can get blocked which can cut off the blood supply to the heart or brain leading to a heart attack or a stroke. By lowering your cholesterol levels, you can reduce your risk of having a heart attack, a stroke or related health problems.

You need to keep taking Crestor, even if it has got your cholesterol to the right level, because it prevents your cholesterol levels from creeping up again and causing build-up of fatty deposits. However, you should stop if your doctor tells you to do so, or you have become pregnant.

 


 Do not take Crestor:

  • If you have ever had an allergic reaction to Crestor, or to any of its ingredients.
  • If you are pregnant or breast-feeding. If you become pregnant while taking Crestor stop taking it immediately and tell your doctor. Women should avoid becoming pregnant while taking Crestor by using suitable contraception.
  • If you have liver disease.
  • If you have severe kidney problems.
  • If you have repeated or unexplained muscle aches or pains.
  • If you take a drug combination of sofosbuvir/velpatasvir/voxilaprevir (used for viral infection of the liver called hepatitis C).
  • If you take a drug called ciclosporin (used, for example, after organ transplants).

If any of the above applies to you (or you are in doubt), please go back and see your doctor.

In addition, do not take Crestor 40 mg (the highest dose):

  • If you have moderate kidney problems (if in doubt, please ask your doctor).
  • If your thyroid gland is not working properly.
  • If you have had any repeated or unexplained muscle aches or pains, a personal or family history of muscle problems, or a previous history of muscle problems when taking other cholesterol-lowering medicines.
  • If you regularly drink large amounts of alcohol.
  • If you are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean and Indian).
  • If you take other medicines called fibrates to lower your cholesterol. 

If any of the above applies to you (or you are in doubt), please go back and see your doctor.

Warnings and precautions

Talk to your doctor or pharmacist before taking Crestor.

  • If you have problems with your kidneys.
  • If you have problems with your liver.
  • If you have had repeated or unexplained muscle aches or pains, a personal or family history of muscle problems, or a previous history of muscle problems when taking other cholesterol-lowering medicines. Tell your doctor immediately if you have unexplained muscle aches or pains, especially if you feel unwell or have a fever. Also, tell your doctor or pharmacist if you have a muscle weakness that is constant.
  • If you have or have had myasthenia (a disease with general muscle weakness including in some cases muscles used when breathing), or ocular myasthenia (a disease-causing eye muscle weakness) as statins may sometimes aggravate the condition or lead to the occurrence of myasthenia (see section 4).
  • If you have ever developed a severe skin rash or skin peeling, blistering and/or mouth sores after taking Crestor or other related medicines.
  • If you regularly drink large amounts of alcohol.
  • If your thyroid gland is not working properly.
  • If you take other medicines called fibrates to lower your cholesterol. Please read this leaflet carefully, even if you have taken other medicines for high cholesterol before.
  • If you take medicines used to treat the HIV infection e.g. ritonavir with lopinavir and/or atazanavir, please see “Other medicines and Crestor”.
  • If you are taking or have taken in the last 7 days a medicine called fusidic acid (a medicine for bacterial infection), orally or by injection. The combination of fusidic acid and Crestor can lead to serious muscle problems (rhabdomyolysis), please see “Other medicines and Crestor”.
  • If you are over 70 (as your doctor needs to choose the right start dose of Crestor to suit you)
  • If you have severe respiratory failure.
  • If you are of Asian origin – that is Japanese, Chinese, Filipino, Vietnamese, Korean and Indian. Your doctor needs to choose the right start dose of Crestor to suit you.

 

If any of the above applies to you (or if you are not sure):

  • Do not take Crestor 40 mg (the highest dose) and check with your doctor or pharmacist before you actually start taking any dose of Crestor.

 

Serious skin reactions including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in association with Crestor treatment. Stop using Crestor and seek medical attention immediately if you notice any of the symptoms described in section 4.

In a small number of people, statins can affect the liver. This is identified by a simple test which looks for increased levels of liver enzymes in the blood. For this reason, your doctor will usually carry out this blood test (liver function test) before and during treatment with Crestor.

While you are on this medicine your doctor will monitor you closely if you have diabetes or are at risk of developing diabetes. You are likely to be at risk of developing diabetes if you have high levels of sugars and fats in your blood, are overweight and have high blood pressure.

 

Children and adolescents

  • If the patient is under 6 years old: Crestor should not be given to children younger than 6 years.
  • If the patient is below 18 years of age: The Crestor 40 mg tablet is not suitable for use in children and adolescents below 18 years of age.

 

Other medicines and Crestor

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

Tell your doctor if you are taking any of the following:

  • ciclosporin (used for example, after organ transplants),
  • warfarin, clopidogrel or ticagrelor (or any other drug used for thinning the blood),
  • fibrates (such as gemfibrozil, fenofibrate) or any other medicine used to lower cholesterol (such as ezetimibe),
  • indigestion remedies (used to neutralise acid in your stomach),
  • erythromycin (an antibiotic), fusidic acid (an antibiotic – please see below and Warnings and precautions),
  • an oral contraceptive (the pill),
  • regorafenib (used to treat cancer),
  • darolutamide (used to treat cancer),
  • capmatinib (used to treat cancer),
  • hormone replacement therapy,
  • fostamatinib (used to treat low platelet counts),
  • febuxostat (used to treat and prevent high blood levels of uric acid),
  • teriflunomide (used to treat multiple sclerosis),
  • any of the following drugs used to treat viral infections, including HIV or hepatitis C infection, alone or in combination (please see Warnings and precautions): ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.

The effects of these medicines could be changed by Crestor or they could change the effect of Crestor.

If you need to take oral fusidic acid to treat a bacterial infection you will need to temporarily stop using this medicine. Your doctor will tell you when it is safe to restart Crestor. Taking Crestor with fusidic acid may rarely lead to muscle weakness, tenderness or pain (rhabdomyolysis). See more information regarding rhabdomyolysis in Section 4.

 

Pregnancy and breast-feeding

Do not take Crestor if you are pregnant or breast-feeding. If you become pregnant while taking Crestor stop taking it immediately and tell your doctor. Women should avoid becoming pregnant while taking Crestor by using suitable contraception.

Ask your doctor or pharmacist for advice before taking any medicine.

 

Driving and using machines

Most people can drive a car and operate machinery while using Crestor – it will not affect their ability. However, some people feel dizzy during treatment with Crestor. If you feel dizzy, consult your doctor before attempting to drive or use machines.

 

Crestor contains lactose.

If you have been told by your doctor that you have an intolerance to some sugars (lactose or milk sugar), contact your doctor before taking Crestor.

For a full list of ingredients, please see Contents of the pack and other information.

 


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

Usual doses in adults

If you are taking Crestor for high cholesterol:

Starting dose

Your treatment with Crestor must start with the 5 mg or the 10 mg dose, even if you have taken a higher dose of a different statin before. The choice of your start dose will depend upon:

  • Your cholesterol levels.
  • The level of risk you have of experiencing a heart attack or stroke.
  • Whether you have a factor that may make you more sensitive to possible side effects.

Please check with your doctor or pharmacist which start dose of Crestor will best suit you.

Your doctor may decide to give you the lowest dose (5 mg) if:

  • You are of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean and Indian).
  • You are over 70 years of age.
  • You have moderate kidney problems.
  • You are at risk of muscle aches and pains (myopathy).

 

Increasing the dose and maximum daily dose

Your doctor may decide to increase your dose. This is so that you are taking the amount of Crestor that is right for you. If you started with a 5 mg dose, your doctor may decide to double this to 10 mg, then 20 mg and then 40 mg if necessary. If you started on 10 mg, your doctor may decide to double this to 20 mg and then 40 mg if necessary. There will be a gap of four weeks between every dose adjustment.

 

The maximum daily dose of Crestor is 40 mg. It is only for patients with high cholesterol levels and a high risk of heart attacks or stroke whose cholesterol levels are not lowered enough with 20 mg.

 

If you are taking Crestor to reduce your risk of having a heart attack, stroke or related health problems:

The recommended dose is 20 mg daily. However, your doctor may decide to use a lower dose if you have any of the factors mentioned above.

 

Use in children and adolescents aged 6-17 years

The dose range in children and adolescents aged 6 to 17 years is 5 to 20 mg once daily. The usual start dose is 5 mg per day, and your doctor may gradually increase your dose to find the right amount of Crestor for you. The maximum daily dose of Crestor is 10 or 20 mg for children aged 6 to 17 years depending on your underlying condition being treated. Take your dose once a day. Crestor 40 mg tablet should not be used by children.

 

Taking your tablets

Swallow each tablet whole with a drink of water.

 

Take Crestor once daily. You can take it at any time of the day with or without food.

 

Try to take your tablet at the same time every day to help you to remember it.

 

Regular cholesterol checks

It is important to go back to your doctor for regular cholesterol checks, to make sure your cholesterol has reached and is staying at the correct level.

Your doctor may decide to increase your dose so that you are taking the amount of Crestor that is right for you. 

 

If you take more Crestor than you should

Contact your doctor or nearest hospital for advice.

If you go into hospital or receive treatment for another condition, tell the medical staff that you’re taking Crestor.

 

If you forget to take Crestor

Don’t worry, just take your next scheduled dose at the correct time. Do not take a double dose to make up for a forgotten dose.

 

If you stop taking Crestor

Talk to your doctor if you want to stop taking Crestor. Your cholesterol levels might increase again if you stop taking Crestor.

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.

It is important that you are aware of what these side effects may be. They are usually mild and disappear after a short time.

Stop taking Crestor and seek medical help immediately if you have any of the following allergic reactions:

  • Difficulty in breathing, with or without swelling of the face, lips, tongue and/or throat.
  • Swelling of the face, lips, tongue and/or throat, which may cause difficulty in swallowing.
  • Severe itching of the skin (with raised lumps).
  • Reddish non-elevated, target-like or circular patches on the trunk, often with central blisters, skin peeling, ulcers of mouth, throat, nose, genitals and eyes. These serious skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
  • Widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).


Also, stop taking Crestor and talk to your doctor immediately:

  • If you have any unusual aches or pains in your muscles which go on for longer than you might expect. Muscle symptoms are more common in children and adolescents than in adults. As with other statins, a very small number of people have experienced unpleasant muscle effects and rarely these have gone on to become a potentially life threatening muscle damage known as rhabdomyolysis.
  • If you experience muscle rupture.
  • If you have lupus-like disease syndrome (including rash, joint disorders and effects on blood cells).

 

Common possible side effects (these may affect between 1 in 10 and 1 in 100 patients):

  • Headache, stomach pain, constipation, feeling sick, muscle pain, feeling weak, dizziness.
  • An increase in the amount of protein in the urine - this usually returns to normal on its own without having to stop taking your Crestor tablets (only Crestor 40 mg).
  • Diabetes. This is more likely if you have high levels of sugars and fats in your blood, are overweight and have high blood pressure. Your doctor will monitor you while you are taking this medicine.

 

Uncommon possible side effects (these may affect between 1 in 100 and 1 in 1,000 patients):

  • Rash, itching or other skin reactions.
  • An increase in the amount of protein in the urine - this usually returns to normal on its own without having to stop taking your Crestor tablets (only Crestor 5 mg, 10 mg and 20 mg).

 

Rare possible side effects (these may affect between 1 in 1,000 and 1 in 10,000 patients):

  • Severe allergic reaction – signs include swelling of the face, lips, tongue and/or throat, difficulty in swallowing and breathing, a severe itching of the skin (with raised lumps). If you think you are having an allergic reaction, then stop taking Crestor and seek medical help immediately.
  • Muscle damage in adults – as a precaution, stop taking Crestor and talk to your doctor immediately if you have any unusual aches or pains in your muscles which go on for longer than expected.
  • A severe stomach pain (inflamed pancreas).
  • Increase in liver enzymes in the blood.
  • Bleeding or bruising more easily than normal due to low level of blood platelets.
  • Lupus-like disease syndrome (including rash, joint disorders and effects on blood cells).

 

Very rare possible side effects (these may affect less than 1 in 10,000 patients):

  • Jaundice (yellowing of the skin and eyes), hepatitis (an inflamed liver), traces of blood in your urine, damage to the nerves of your legs and arms (such as numbness), joint pain, memory loss and breast enlargement in men (gynaecomastia).

 

Side effects of unknown frequency may include:

  • Diarrhoea (loose stools), cough, shortness of breath, oedema (swelling), sleep disturbances, including insomnia and nightmares, sexual difficulties, depression, breathing problems, including persistent cough and/or shortness of breath or fever, tendon injury and muscle weakness that is constant.
  • Myasthenia gravis (a disease causing general muscle weakness including in some cases muscles used when breathing), Ocular myasthenia (a disease causing eye muscle weakness). Talk to your doctor if you experience weakness in your arms or legs that worsens after periods of activity, double vision or drooping of your eyelids, difficulty swallowing, or shortness of breath.

  •  Blisters: Store below 30°C. Store in the original package in order to protect from moisture.
  •  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 box/blisters/label after EXP. The expiry date refers to the last day of the month.
  •  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 substance in Crestor is rosuvastatin. Crestor film-coated tablets contain rosuvastatin calcium equivalent to 5 mg, 10 mg, 20 mg or 40 mg of rosuvastatin. The other ingredients are: lactose monohydrate, microcrystalline cellulose, calcium phosphate, crospovidone, magnesium stearate, hypromellose, triacetin, titanium dioxide (E171). Crestor 10 mg, 20 mg and 40 mg film-coated tablets also contain red iron oxide (E172). Crestor 5 mg film-coated tablets also contain yellow iron oxide (E172).

 


Crestor comes in blister packs containing 7, 14, 15, 20, 28, 30, 42, 50, 56, 60, 84, 90, 98 and 100 tablets and plastic containers with 30 and 100 tablets (Not all packs are available in every country). Crestor 10 mg film-coated tablets are pink, round and marked with ZD4522 and 10 on one side and plain on the reverse. Crestor 20 mg film-coated tablets are pink, round and marked with ZD4522 and 20 on one side and plain on the reverse.

The Marketing Authorisations Holder

AstraZeneca UK Ltd,

600 Capability Green, Luton,

LU1 3LU, UK.

 

Manufacturers

IPR Pharmaceuticals Incorporated    

Road 188, Lot 17,

San Isidro industrial Park Canovanas.

PR00729 - USA


July 2023
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

ينتمي عقار كريستور إلى مجموعة من الأدوية يُطلق عليها الستاتينيات.

تم وصف عقار كريستور لك بسبب:

  •  ارتفاع مستوى الكوليسترول لديك. وهذا يعني أنك تواجه خطر التعرض لنوبة قلبية أو سكتة دماغية. يُستخدم عقار كريستور للبالغين والمراهقين والأطفال بعمر 6 أعوام أو الأكبر سنًا لعلاج ارتفاع مستوى الكوليسترول.
  • لذا ننصحك بتناول أحد أدوية الستاتينيات، لأن تغيير النظام الغذائي الخاص بك وممارسة المزيد من التمرينات الرياضية لم يعُدا كافيين للرجوع بمستويات الكوليسترول إلى المستويات الطبيعية. ينبغي عليك الاستمرار في اتباع نظام غذائي يخفّض مستوى الكوليسترول إلى جانب ممارسة التمرينات الرياضية أثناء فترة استخدام عقار كريستور.

أو

 

  • إصابتك بعوامل أخرى تزيد من خطر تعرّضك لنوبة قلبية أو سكتة دماغية أو مشاكل صحية ذات صلة.

 

من الممكن أن تتسبب الإصابة بمرض تصلب الشرايين في نوبة قلبية وسكتة دماغية ومشاكل صحية أخرى. ويحدث تصلب الشرايين بسبب تراكم الرواسب الدهنية داخل الشرايين.

 

ما أهمية الاستمرار في تناول عقار كريستور

يُستخدم كريستور في تصحيح مستويات المواد الدهنية في الدم والتي يُطلق عليها الشحوم، وأكثرها شيوعًا هو الكوليسترول.

 

ثمة أنواع مختلفة من الكوليسترول توجد بالدم – الكوليسترول "الضار" (LDL-C) والكوليسترول "النافع" (HDL-C).

 

  •  يستطيع عقار كريستور أن يقلل من نسبة الكوليسترول الضار ويزيد من نسبة الكوليسترول النافع.
  •  فهو يساعد على منع جسمك من إنتاج الكوليسترول "الضار". كما يعمل على تحسين قدرة الجسم على إخراجه من دمك.

بالنسبة لمعظم الناس، لا يؤدي ارتفاع مستويات الكوليسترول إلى ظهور أي أعراض يمكنهم أن يشعروا بها. ومع ذلك، إذا تُرك ارتفاع مستويات الكوليسترول من دون معالجة، فقد تتراكم الرواسب الدهنية داخل جدران الأوعية الدموية، مما يؤدي إلى تضيقها.

 

وفي بعض الأحيان، قد يحدث انسداد بالأوعية الدموية الضيقة وهو ما قد يوقف تدفق الدم إلى القلب والمخ مما يؤدي إلى الإصابة بنوبة قلبية أو سكتة دماغية. وبتقليل مستويات الكوليسترول لديك، يمكنك الحد من خطر الإصابة بنوبة قلبية أو سكتة دماغية أو المشاكل الصحية ذات الصلة.

 

من الضروري أن تستمر في تناول عقار كريستور، حتى لو وصل بالكوليسترول إلى المستوى المناسب، لأنه يمنع مستويات الكوليسترول من الارتفاع مرة أخرى والتسبب في تراكم الرواسب الدهنية. ولكن ينبغي عليك إيقاف تناول العقار إذا أخبرك الطبيب بذلك أو في حال حدوث حمل.

 

لا تتناول عقار كريستور:

  • إذا سبق أن تعرضت لأي رد فعل تحسسي تجاه عقار كريستور، أو لأي من مكوناته.
  • إذا كنتِ حاملاً أو تُرضعين طبيعيًا. إذا أصبحتِ حاملاً أثناء فترة استخدام عقار كريستور، فأوقفيه على الفور وأخبري طبيبكِ بذلك. ينبغي أن تتجنب السيدات الحمل أثناء فترة استخدام كريستور وذلك باستخدام الوسائل المناسبة لمنع الحمل.
  • إذا كنت تعاني من مرض بالكبد.
  • إذا كنت تعاني من مشاكل شديدة في الكلى.
  • إذا كنت تعاني من آلام أو أوجاع عضلية متكررة أو غير مبررة.
  • إذا كنت تتناول توليفة من عقار سوفوسبوفير/فلباتاسفير/فوكسيلابريفير (المستخدم لعلاج العدوى الفيروسية للكبد التي تُسمى التهاب الكبد الوبائي ج).
  • إذا كنت تتناول عقارًا باسم سايكلوسبورين (يُستخدم، على سبيل المثال، بعد عمليات زراعة الأعضاء).

إذا انطبق عليك أي مما سبق (أو ساورك أي شك)، فيُرجى الرجوع إلى طبيبك.

 

بالإضافة إلى ذلك، تجنب تناول كريستور 40 ملجم (أعلى جرعة):

  • إذا كنت تعاني من قصور كلوي متوسط (إذا ساورك أي شك، فيُرجى الرجوع إلى طبيبك).
  • إذا كانت الغدة الدرقية لديك لا تعمل على النحو الصحيح.
  • إذا قد كنت تعاني من أوجاع أو آلام عضلية متكررة أو غير مبررة، أو أن تكون قد تعرضت أنت أو أي من أفراد عائلتك في السابق لأي مشاكل عضلية بصفة عامة أو عند تناول أدوية أخرى خافضة للكوليسترول.
  • إذا كنت تتناول الكحول بإفراط.
  • إذا كنت من أصول آسيوية (ياباني، وصيني، وفلبيني، وفييتنامي، وكوري، وهندي).
  • إذا كنت تتناول أدوية أخرى يُطلق عليها الفيبرات لخفض نسبة الكوليسترول لديك.

إذا انطبق عليك أي مما سبق (أو ساورك أي شك)، فيُرجى الرجوع إلى طبيبك.

 

تحذيرات واحتياطات

 

عليك مشاورة طبيبك أو الصيدلي قبل تناول عقار كريستور.

  • إذا كنت تعاني من مشاكل بالكلى.
  • إذا كنت تعاني من مشاكل بالكبد.
  • إذا قد كنت تعاني من أوجاع أو آلام عضلية متكررة أو غير مبررة، أو أن تكون قد تعرضت أنت أو أي من أفراد عائلتك في السابق لأي مشاكل عضلية بصفة عامة أو عند تناول أدوية أخرى خافضة للكوليسترول. أخبر طبيبك فورًا بما إذا كنت تعاني من أوجاع أو آلام عضلية غير مبررة وخصوصًا إذا كنت تشعر بتوعك أو مصابًا بحمى. كما يجب أن تخبر طبيبك أو الصيدلي بما إذا كنت تعاني من ضعف عضلي بشكل دائم.
  • إذا كنت مصابًا أو كنت مصابًا بالوهن العضلي (مرض مع ضعف عام للعضلات بما في ذلك في بعض الحالات العضلات المستخدمة عند التنفس) ، أو الوهن العضلي العيني (مرض يسبب ضعف عضلات العين) ، فقد تؤدي الستاتينات أحيانًا إلى تفاقم الحالة أو تؤدي إلى حدوث الوهن العضلي (انظر القسم 4).
  • إذا كنت قد أُصبت قبل ذلك بطفح جلدي شديد أو تقشر في الجلد، و/أو بثور و/أو قرح في الفم بعد تناول كريستور أو أي أدوية أخرى ذات صلة.
  • إذا كنت تتناول الكحول بإفراط بشكل منتظم.
  • إذا كانت الغدة الدرقية لديك لا تعمل على النحو الصحيح.
  • إذا كنت تتناول أدوية أخرى يُطلق عليها الفيبرات لخفض نسبة الكوليسترول لديك. يُرجى قراءة هذا المنشور بعناية، حتى لو كنت قد تناولت أدوية أخرى قبل ذلك لعلاج ارتفاع مستوى الكوليسترول.
  • في حالة تناول الأدوية المستخدمة في علاج عدوى الإيدز (HIV) مثل ريتونافير مع لوبينافير و/أو أتازانافير، يُرجى الاطلاع على قسم "الأدوية الأخرى وكريستور".
  • إذا كنت تتناول أو قد تناولت في الأيام السبعة الماضية دواءً يُسمى حمض الفوسيديك (دواء لعلاج العدوى البكتيرية)، فمويًا أو عن طريق الحقن. يمكن أن يؤدي الجمع بين حمض الفوسيديك وعقار كريستور إلى مشكلات خطيرة في العضلات (انحلال الربيدات)، يُرجى الاطلاع على قسم "الأدوية الأخرى وكريستور".
  • إذا كان عمرك أكثر من 70 عامًا (حيث يحتاج طبيبك تحديد جرعة البدء المناسبة من كريستور بما يلائم حالتك)
  • إذا كنت مصابًا بفشل تنفسي شديد.
  • إذا كنت من أصول آسيوية – سواء ياباني، وصيني، وفلبيني، وفييتنامي، وكوري، وهندي. يحتاج طبيبك إلى تحديد جرعة البدء المناسبة من كريستور بما يلائم حالتك.

إذا انطبق عليك أي من الحالات السابقة (أو إذا ساورك أي شك):

  •  يجب عدم تناول كريستور 40 ملجم (أعلى جرعة) والرجوع إلى الطبيب أو الصيدلي قبل أن تبدأ فعليًا في تناول أي جرعة من كريستور.

تم الإبلاغ عن ردود فعل جلدية خطيرة بما في ذلك متلازمة ستيفنز جونسون وتفاعلات دوائية مع كثرة اليوزينيات والأعراض الجهازية (DRESS) عند العلاج بعقار كريستور. توقف عن استخدام كريستور واطلب الرعاية الطبية فورًا إذا لاحظت أيًا من الأعراض المذكورة في القسم 4.

 

تؤثر الستاتينيات على الكبد في عدد قليل من الأشخاص. ويتحدد هذا بإجراء اختبار بسيط يكشف عن المستويات الزائدة من إنزيمات الكبد في الدم. ولهذا السبب، سيجُري لك الطبيب اختبار الدم هذا (اختبار وظائف الكبد) قبل تلقي العلاج بكريستور وأثناء فترة تلقيه.

 

أثناء فترة استخدام هذا الدواء، سيتابع الطبيب حالتك عن كثب إذا كنت مصابًا بمرض السكري أو معرّضًا للإصابة به. من المرجح أن تتعرض للإصابة بمرض السكري إذا كنت تعاني من مستويات مرتفعة من السكر والدهون في الدم، أو كنت تعاني من وزن زائد وارتفاع ضغط الدم.

 

الأطفال والمراهقون

  • إذا كان عمر المريض أقل من 6 سنوات: ينبغي ألا يُعطى عقار كريستور للأطفال ممن تقل أعمارهم عن 6 أعوام.
  • إذا كان عمر المريض أقل من 18 عامًا: لا يُعد كريستور 40 ملجم مناسبًا للاستخدام عند الأطفال والمراهقين الذين تقل أعمارهم عن 18 عامًا.

 

 

الأدوية الأخرى وكريستور

أخبر طبيبك أو الصيدلي بما إذا كنت تتناول، أو تناولت مؤخرًا أو قد تتناول أيّة أدوية أخرى

 

أخبر طبيبك بما إذا كنت تتناول أيًا مما يلي:

  • سايكلوسبورين (يُستخدم، على سبيل المثال، بعد عمليات زراعة الأعضاء)،
  • وارفارين أو كلوبيدوغريل أو تيكاجريلور (أو أي عقار آخر يُستخدم لترقيق الدم)،
  • الفيبرات (مثل جمفبروزيل، فينوفيبرات) أو أي دواء آخر يُستخدم لخفض الكوليسترول (مثل إزيتمايب)،
  • علاجات عسر الهضم (تُستخدم لتحييد الحمض في معدتك)،
  • إريثرومايسين (مضاد حيوي)، حمض الفوسيديك (مضاد حيوي - يُرجى الاطلاع أدناه وعلى التحذيرات والاحتياطات)،
  • موانع الحمل الفموية (الحبوب)،
  •  ريجورافينيب (يُستخدم لعلاج السرطان)،
  • دارولوتاميد (يُستخدم لعلاج السرطان)،
  • كابماتينيب (يُستخدم لعلاج السرطان)،
  • العلاج بالهرمونات البديلة،
  • فوستاماتينيب (يُستخدم لعلاج انخفاض عدد الصفائح الدموية)،
  • فيبوكسوستات (يُستخدم لعلاج ارتفاع مستويات حمض اليوريك في الدم والوقاية منها)،
  • تيريفلونوميد (يُستخدم لعلاج التصلب المتعدد)،
  • أي من العقاقير التالية المستخدمة لعلاج العداوى الفيروسية، بما في ذلك فيروس نقص المناعة البشرية أو عدوى التهاب الكبد الوبائي ج، بمفردها أو جنبًا إلى جنب مع أدوية أخرى (يُرجى الاطلاع على التحذيرات والاحتياطات): ريتونافير، لوبينافير، أتازانافير، سوفوسبوفير، فوكسيلابريفير، أمبيتاسفير، باريتابريفير، داسابوفير، فلباتاسفير، غرازوبريفير، إلباسفير، غليكابريفير، بيبرنتاسفير.

قد يتغير مفعول هذه الأدوية بسبب تناول كريستور أو قد تُغيّر من مفعول كريستور.

 

إذا كنت بحاجة إلى تناول حمض الفوسيديك الفموي لعلاج عدوى بكتيرية، فسوف يتعين عليك التوقف مؤقتًا عن استخدام هذا الدواء. وسيخبرك طبيبك بالتوقيت الآمن لبدء استخدام كريستور من جديد. نادرًا ما يؤدي تناول عقار كريستور مع حمض الفوسيديك إلى ضعف أو إيلام أو ألم في العضلات (انحلال الربيدات). راجع المزيد من المعلومات حول انحلال الربيدات في القسم 4.

 

الحمل والإرضاع الطبيعي

 

لا تتناولي كريستور إذا كنتِ حاملاً، أو تُرضعين طبيعيًا. إذا أصبحتِ حاملاً أثناء فترة استخدام عقار كريستور، فأوقفيه على الفور وأخبري طبيبكِ بذلك. ينبغي أن تتجنب السيدات الحمل أثناء فترة استخدام كريستور وذلك باستخدام الوسائل المناسبة لمنع الحمل.

 

استشيري طبيبكِ أو الصيدلي قبل تناول أي دواء.

 

القيادة واستخدام الآلات

يستطيع معظم الأشخاص قيادة السيارة وتشغيل الآلات أثناء استخدام عقار كريستور – فهو لا يؤثر على قدرتهم. ومع ذلك، فبعض الأشخاص يشعرون بالدوار أثناء العلاج بعقار كريستور. إذا شعرت بالدوار، فيجب عليك استشارة الطبيب قبل محاولة القيادة أو استخدام الآلات.

 

يحتوي كريستور على اللاكتوز.

إذا أخبرك طبيبك بأنّك لا تحتمل بعض أنواع السكر (اللاكتوز أو سكر الحليب)، فعليك الاتصال به قبل تناول عقار كريستور.

للحصول على قائمة كاملة بمكوناته، يُرجى الاطلاع على محتويات العبوة ومعلومات أخرى.

https://localhost:44358/Dashboard

عليك دومًا تناول هذا الدواء وفقًا لتوجيهات الطبيب. استشر الطبيب المتابع لك أو الصيدلي إذا كانت تساورك أي شكوك.

 

الجرعات المعتادة بالنسبة للبالغين

إذا كنت تتناول كريستور لعلاج ارتفاع الكوليسترول:

جرعة البدء

 

يجب أن تبدأ علاجك باستخدام كريستور بجرعة 5 ملجم أو 10 ملجم، حتى لو كنت قد تناولت قبل ذلك جرعة أعلى من نوع مختلف من الستاتينات. سيعتمد اختيار جرعة البدء على ما يلي:

  • مستويات الكوليسترول لديك.
  • مستوى خطر إمكانية تعرضك للإصابة بنوبة قلبية أو سكتة قلبية.
  • ما إذا كان لديك عامل قد يجعلك أكثر عرضة للإصابة بالآثار الجانبية المحتملة.

 

يُرجى الرجوع إلى طبيبك أو الصيدلي لمعرفة جرعة البدء الأنسب لك من عقار كريستور.

 

وقد يقرر طبيبك إعطاءك أقل جرعة (5 ملجم) إذا:

  • كنت من أصول آسيوية (ياباني، وصيني، وفلبيني، وفييتنامي، وكوري، وهندي).
  • كان عمرك أكثر من 70 عامًا.
  • كنت تعاني من مشاكل متوسطة بالكلى.
  • كنت معرضًا للإصابة بأوجاع وآلام عضلية (اعتلال عضلي).

 

زيادة الجرعة والحد الأقصى من الجرعة اليومية

قد يقرر طبيبك زيادة جرعتك. وذلك حتى تتلقى الجرعة الأنسب لك من عقار كريستور. إذا بدأت بجرعة 5 ملجم، فقد يقرر طبيبك مضاعفة الجرعة إلى 10 ملجم، ثم إلى 20 ملجم وبعد ذلك إلى 40 ملجم إذا لزم الأمر. أما إذا بدأت بجرعة 10 ملجم، فقد يقرر طبيبك مضاعفة الجرعة إلى 20 ملجم وبعد ذلك إلى 40 ملجم إذا لزم الأمر. وسيكون هناك فترة زمنية فاصلة تُقدر بأربعة أسابيع بين كل تعديل للجرعة.

 

تبلغ الجرعة اليومية القصوى من عقار كريستور 40 ملجم. لا تُعطى هذه الجرعة القصوى إلا للمرضى الذين يعانون من مستويات مرتفعة من الكوليسترول والمعرضين بشكل كبير لخطر الإصابة بنوبات قلبية أو سكتة دماغية ممن لا تنخفض مستويات الكوليسترول لديهم بدرجة كافية باستخدام جرعة 20 ملجم.

 

إذا كنت تتناول عقار كريستور لتقليل خطر الإصابة بنوبة قلبية أو سكتة دماغية أو مشاكل صحية ذات صلة:

الجرعة اليومية المُوصى بها هي 20 ملجم. ومع ذلك، فقد يقرر طبيبك استخدام جرعة أقل إذا كنت تعاني من أي من العوامل المذكورة أعلاه.

 

الاستخدام مع الأطفال والمراهقين الذين تتراوح أعمارهم بين 6 و17 عامًا

يتراوح نطاق الجرعة لدى الأطفال والمراهقين الذين تتراوح أعمارهم بين 6 و17 عامًا بين 5 و20 ملجم مرة واحدة يوميًا. تبلغ جرعة البدء الاعتيادية 5 ملجم، وقد يُزيد طبيبك الجرعة تدريجيًا حتى يصل إلى الجرعة المناسبة لك من عقار كريستور. تبلغ الجرعة اليومية القصوى من عقار كريستور 10 أو 20 ملجم للأطفال الذين تتراوح أعمارهم بين 6 و17 عامًا اعتمادًا على الحالة المرضية التي يتم علاجها. تناول جرعتك مرة واحدة يوميًا. يجب عدم استخدام أقراص كريستور 40 ملجم من قِبل الأطفال.

 

تناول الأقراص

ابتلع القرص كاملاً مع شرب الماء.

 

تناول كريستور مرة واحدة يوميًا. ويمكنك تناوله في أي وقت من اليوم مع الطعام أو دونه.

 

حاول أن تتناول القرص في الوقت نفسه يوميًا كي يمكنك تذكره.

 

فحوصات الكوليسترول المنتظمة

من الضروري الرجوع إلى طبيبك لإجراء فحوصات كوليسترول منتظمة، للتأكد من وصول الكوليسترول إلى المستوى المناسب والحفاظ على هذا المستوى.

 

قد يقرر طبيبك زيادة الجرعة كى تتلقى الجرعة المناسبة لك من عقار كريستور.

 

إذا تناولت جرعة من كريستور أكثر مما ينبغي

اتصل بطبيبك أو أقرب مستشفى للحصول على النصيحة الطبية.

 

إذا ذهبت إلى المستشفى أو كنت تتلقى علاجًا لحالة مرضية أخرى، فينبغي إخبار الطاقم الطبي بأنك تتناول كريستور.

 

إذا نسيت تناول كريستور

لا تقلق، ما عليك إلا أن تتناول الجرعة المحددة التالية في موعدها. لا تأخذ جرعة مضاعفة لتعويض أيّ جرعة فائتة.

 

إذا توقفت عن تناول كريستور

تحدث إلى طبيبك إذا كنت ترغب في إيقاف تناول كريستور. قد ترتفع مستويات الكوليسترول مرة أخرى إذا توقفت عن تناول كريستور.

 

إذا كانت لديك أي أسئلة أخرى حول استخدام هذا الدواء، فتحدث إلى طبيبك أو الصيدلي.

قد يُسبِّب هذا الدواء، شأنه شأن جميع الأدوية، آثارًا جانبية، على الرغم من أنها لا تصيب الجميع.

 

من المهم معرفة طبيعة تلك الآثار الجانبية. فهي عادةً تكون بسيطة وتزول بعد وقت قليل.

 

توقف عن تناول كريستور واطلب المساعدة الطبية فورًا إذا أصبت بأي من ردود الفعل التحسسية التالية:

  • صعوبة في التنفس مصحوبة أو غير مصحوبة بتورم الوجه و/أو الشفتين و/أو اللسان و/أو الحلق.
  • تورم الوجه و/أو الشفتين و/أو اللسان و/أو الحلق، الأمر الذي قد يؤدي إلى صعوبة في البلع.
  • حكة جلدية شديدة (مصحوبة ببثور بارزة).
  • بقع حمراء غير مرتفعة أو تشبه علامة التصويب أو دائرية على الجذع، غالبًا مصحوبة ببثور مركزية، وتقشر الجلد، وتقرحات بالفم والحلق والأنف والأعضاء التناسلية والعينين. يمكن أن يسبق حالات الطفح الجلدي الخطيرة هذه الحمى وأعراض تشبه أعراض الإنفلونزا [متلازمة ستيفنز جونسون).
  • طفح جلدي واسع الانتشار، وارتفاع درجة حرارة الجسم، وتضخم العقد الليمفاوية (متلازمة DRESS أو متلازمة فرط التحسس للدواء).


توقف أيضًا عن تناول كريستور وتحدث إلى طبيبك على الفور:

 

  • إذا كنت تعاني من أي أوجاع أو آلام غير معتادة في عضلاتك استمرت لفترة أطول مما تتوقع. وتظهر الأعراض العضلية بدرجة أكبر في الأطفال والمراهقين عن البالغين. كما هو الحال مع أدوية الستاتينيات الأخرى، هناك عدد قليل جدًا من الأشخاص يعانون من آثار عضلية مزعجة ونادرًا ما تتطور هذه الأعراض لتتحول إلى تلف عضلي محتمل مهدد للحياة وهو ما يُعرف باسم انحلال الربيدات.
  • إذا كنت تعاني من تمزق العضلات.
  • إذا كنت تعاني من متلازمة شبيهة بمرض الذئبة (بما في ذلك الطفح الجلدي واضطرابات المفاصل وتأثيرات على خلايا الدم).

 

الآثار الجانبية المحتملة الشائعة (قد تظهر هذه الآثار لدى مريض واحد من بين 10 مرضى ومريض واحد من بين 100 مريض):

  • صداع، ألم في المعدة، إمساك، شعور بالإعياء، ألم في العضلات، شعور بالضعف، دوخة.
  • زيادة نسبة البروتين في البول - وتعود هذه النسبة إلى معدلها الطبيعي دون الاضطرار إلى إيقاف تناول أقراص كريستور (كريستور 40 ملجم فقط).
  • مرض السكري. من المرجح الإصابة بمرض السكري إذا كنت تعاني من مستويات مرتفعة من السكر والدهون في الدم، أو كنت تعاني من وزن زائد وارتفاع ضغط الدم. سيتابع طبيبك حالتك أثناء فترة استخدام هذا الدواء.

 

الآثار الجانبية المحتملة غير الشائعة (قد تظهر هذه الآثار لدى مريض واحد من بين 100 مريض ومريض واحد من بين 1000 مريض):

  • طفح جلدي أو حكة أو غيرهما من ردود الفعل الجلدية.
  • زيادة نسبة البروتين في البول - وتعود هذه النسبة إلى معدلها الطبيعي دون الاضطرار إلى إيقاف تناول أقراص كريستور (كريستور 5 ملجم و10 ملجم و20 ملجم فقط).

 

الآثار الجانبية المحتملة النادرة (قد تظهر هذه الآثار لدى مريض واحد من بين 1000 مريض ومريض واحد من بين 10000 مريض):

  • رد فعل تحسسي شديد – تتضمن العلامات حدوث تورم للوجه و/أو الشفتين و/أو اللسان و/أو الحلق، وصعوبة في البلع والتنفس، وحكة جلدية شديدة (مصحوبة ببثور بارزة). إذا كنت تعتقد أنك تعاني من رد فعل تحسسي، فعليك إيقاف تناول كريستور وطلب المساعدة الطبية فورًا.
  •  تلف عضلي لدى البالغين – على سبيل الاحتياط، أوقف تناول كريستور وتحدث إلى طبيبك فورًا إذا كنت تعاني من أوجاع أو آلام عضلية غير معتادة استمرت لمدة أطول من المتوقع.
  • ألم شديد في المعدة (التهاب البنكرياس).
  • ارتفاع إنزيمات الكبد في الدم.
  • نزف أو تكدّم يحدث بسهولة تفوق المعتاد بسبب انخفاض مستوى الصفائح الدموية.
  • متلازمة شبيهة بمرض الذئبة (تشمل الطفح الجلدي واضطرابات المفاصل وتأثيرات على خلايا الدم). 

 

آثار جانبية محتملة نادرة جدًا (قد تظهر هذه الآثار على أقل لدى مريض واحد من بين 10000 مريض):

  •  اليرقان (اصفرار الجلد والعينين)، والتهاب الكبد، ومقدار ضئيل من الدم في البول، وتلف أعصاب الساقين والذراعين (مثل الخدر)، وألم المفاصل، وفقدان الذاكرة وتضخم الثدي لدى الرجال (تثدي الرجل).

قد تحدث آثار جانبية بمعدل تكرار غير معروف تشمل ما يلي:

  • إسهال (براز رخو)، وسعال، وضيق في التنفس، ووذمة (تورم)، واضطرابات في النوم، تشمل الأرق والكوابيس، ومشكلات جنسية، واكتئاب، ومشاكل في التنفس، بما في ذلك سعال مستمر و/أو ضيق في التنفس أو حمّى، وإصابة بالوتر وضعف عضلي مستمر.
  • الوهن العضلي (وهو ضعف عام للعضلات يسبب المرض بما في ذلك العضلات المستخدمة عند التنفس في بعض الحالات) ، الوهن العضلي العيني (مرض يسبب ضعف عضلات العين). تحدث إلى طبيبك إذا كنت تعاني من ضعف في ذراعيك أو ساقيك يزداد سوءًا بعد فترات من النشاط أو ازدواج الرؤية أو تدلي الجفون أو صعوبة البلع أو ضيق التنفس.
  • شرائط الدواء: تحفظ في درجة حرارة أقل من 30 درجة مئوية. تحفظ في العبوة الأصلية للحماية من الرطوبة.
  • العبوات: تحفظ في درجة حرارة أقل من 30 درجة مئوية. احتفظ بالزجاجة مغلقة بإحكام شديد لحمايتها من الرطوبة.
  • احفظ هذا الدواء بعيدًا عن مرأى الأطفال ومتناولهم.
  • لا تستخدم هذا الدواء بعد تاريخ انتهاء صلاحيته المدوّن على العلبة/الشرائط/الملصق بعد كلمة EXP. يشير تاريخ انتهاء الصلاحية إلى آخر يوم في الشهر.
  • لا تتخلص من الأدوية في مياه الصرف الصحي أو مكب النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد تستخدمها. ستساعد هذه الإجراءات على حماية البيئة.

 

المادة الفعالة في كريستور هي روزيوفاستاتين. تحتوي أقراص كريستور المغلفة على روزيوفاستاتين الكالسيوم المكافئ لـ 5 ملجم أو 10 ملجم أو 20 ملجم أو 40 ملجم من روزيوفاستاتين. المكونات الأخرى هي: لاكتوز أحادي الهيدرات، سيليلوز بلوري مكروي، فوسفات الكالسيوم، كروسبوفيدون، سترات الماغنيسيوم، هايبروميلوز، ثُلاثيُّ الأَستين، ثُنائي أكسيد التيتانيوم (E171). كما تحتوي أقراص كريستور 10 ملجم و20 ملجم و40 ملجم المغلفة على أكسيد الحديد الأحمر (E172). وتحتوي أقراص كريستور 5 ملجم المغلفة على أكسيد الحديد الأصفر (E172).

 

يأتي كريستور في عبوات من شرائط تحتوي على 7 و14 و15 و20 و28 و30 و42 و50 و56 و60 و84 و90 و98 و100 قرص وحاويات بلاستيكية تحتوي على 30 و100 قرص (لا تتوفر جميع العبوات بجميع الدول).

يأتي كريستور في أقراص بتركيزين:

أقراص كريستور 10 ملجم المغلفة زهرية اللون مستديرة الشكل ومطبوع عليها "ZD4522" والرقم 10 على أحد الجانبين ولا يوجد شيء على الجانب الآخر.

أقراص كريستور 20 ملجم المغلفة زهرية اللون مستديرة الشكل ومطبوع عليها "ZD4522" والرقم 20 على أحد الجانبين ولا يوجد شيء على الجانب الآخر.

حامل ترخيص التسويق

 

AstraZeneca UK Limited

600 CAPABILITY GREEN, LUTON

LU13LU, Luton

المملكة المتحدة

 

 

الجهة المصنّعة

 

IPR Pharmaceuticals Incorporated         

Road 188, Lot 17,

San Isidro industrial Park Canovanas.

PR00729 - الولايات المتحدة الأمريكية

 

يوليو 2023
 Read this leaflet carefully before you start using this product as it contains important information for you

Crestor 10 mg film-coated tablets.

10 mg: Each tablet contains 10 mg rosuvastatin (as rosuvastatin calcium). Each tablet contains 91.3 mg lactose monohydrate. For a full list of excipients, see Section 6.1.

10 mg: Film-coated tablet. Round, pink coloured tablets, intagliated with 'ZD4522' and '10' on one side and plain on the reverse.

Treatment of hypercholesterolaemia

Adults, adolescents and children aged 6 years or older with primary hypercholesterolaemia (type IIa including heterozygous familial hypercholesterolaemia) or mixed dyslipidaemia (type IIb) as an adjunct to diet when response to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is inadequate.

Adults, adolescents and children aged 7 years or older with homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.

Prevention of Cardiovascular Events

Prevention of major cardiovascular events in patients who are estimated to have a high risk for a first cardiovascular event (see section 5.1), as an adjunct to correction of other risk factors.


Before treatment initiation the patient should be placed on a standard

cholesterol-lowering diet that should continue during treatment. The dose should be individualised according to the goal of therapy and patient response, using current consensus guidelines.

Crestor may be given at any time of day, with or without food.

Treatment of hypercholesterolaemia

The recommended start dose is 5 or 10 mg orally once daily in both statin naïve or patients switched from another HMG CoA reductase inhibitor. The choice of start dose should take into account the individual patient’s cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions (see below). A dose adjustment to the next dose level can be made after 4 weeks, if necessary (see section 5.1). In light of the increased reporting rate of adverse reactions with the 40 mg dose compared to lower doses (see section 4.8), a final titration to the maximum dose of 40 mg should only be considered in patients with severe hypercholesterolaemia at high cardiovascular risk (in particular those with familial hypercholesterolaemia), who do not achieve their treatment goal on 20 mg, and in whom routine follow-up will be performed (see

section 4.4). Specialist supervision is recommended when the 40 mg dose is initiated.

Prevention of cardiovascular events

In the cardiovascular events risk reduction study, the dose used was 20 mg daily (see section 5.1).

Paediatric population

Paediatric use should only be carried out by specialists.

 

Children and adolescents 6 to 17 years of age (Tanner Stage <II-V) Heterozygous familial hypercholesterolaemia

In children and adolescents with heterozygous familial hypercholesterolaemia the usual start dose is 5 mg daily.

·     In children 6 to 9 years of age with heterozygous familial hypercholesterolaemia, the usual dose range is 5-10 mg orally once daily. Safety and efficacy of doses greater than 10 mg have not been studied in this population.

·     In children 10 to 17 years of age with heterozygous familial hypercholesterolaemia, the usual dose range is 5-20 mg orally once daily. Safety and efficacy of doses greater than 20 mg have not been studied in this population.

Titration should be conducted according to the individual response and tolerability in paediatric patients, as recommended by the paediatric treatment recommendations (see section 4.4). Children and adolescents should be placed on standard cholesterol-lowering diet before rosuvastatin treatment initiation; this diet should be continued during rosuvastatin treatment.

 

Homozygous familial hypercholesterolaemia

In children 7 to 17 years of age with homozygous familial hypercholesterolaemia, the recommended maximum dose is 20 mg once daily.

A starting dose of 5 to 10 mg once daily depending on age, weight and prior statin use is advised. Titration to the maximum dose of 20 mg once daily should be conducted according to the individual response and tolerability in paediatric patients, as recommended by the paediatric treatment recommendations (see section 4.4). Children and adolescents should be placed on standard cholesterol- lowering diet before rosuvastatin treatment initiation; this diet should be continued during rosuvastatin treatment.

There is limited experience with doses other than 20 mg in this population. The 40 mg tablet is not suitable for use in paediatric patients.

Children younger than 7 years

The safety and efficacy of use in children younger than 7 years has not been studied. Therefore, Crestor is not recommended for use in children younger than 7 years.

 

Use in the elderly

A start dose of 5 mg is recommended in patients >70 years (see section 4.4). No other dose adjustment is necessary in relation to age.

Dosage in patients with renal insufficiency

No dose adjustment is necessary in patients with mild to moderate renal impairment. The recommended start dose is 5 mg in patients with moderate renal impairment (creatinine clearance <60 ml/min). The 40 mg dose is contraindicated in patients with moderate renal impairment. The use of Crestor in patients with severe renal impairment is contraindicated for all doses (see sections 4.3 and 5.2).

Dosage in patients with hepatic impairment

There was no increase in systemic exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below. However, increased systemic exposure has been observed in subjects with Child-Pugh scores of 8 and 9 (see section 5.2). In these patients an assessment of renal function should be considered (see

section 4.4). There is no experience in subjects with Child-Pugh scores above 9. Crestor is contraindicated in patients with active liver disease (see section 4.3).

 

Race

Increased systemic exposure has been seen in Asian subjects (see sections 4.3, 4.4 and 5.2). The recommended start dose is 5 mg for patients of Asian ancestry. The 40 mg dose is contraindicated in these patients.

 

Genetic polymorphisms

Specific types of genetic polymorphisms are known that can lead to increased rosuvastatin exposure (see section 5.2). For patients who are known to have such specific types of polymorphisms, a lower daily dose of Crestor is recommended.

Dosage in patients with pre-disposing factors to myopathy

The recommended start dose is 5 mg in patients with predisposing factors to myopathy (see section 4.4).

The 40 mg dose is contraindicated in some of these patients (see section 4.3).

 

Concomitant therapy

Rosuvastatin is a substrate of various transporter proteins (e.g. OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when Crestor is administered concomitantly with certain medicinal products that may increase the plasma concentration of rosuvastatin due to interactions with these transporter proteins (e.g. ciclosporin and certain protease inhibitors including combinations of ritonavir with atazanavir, lopinavir and/or tipranavir; see sections 4.4 and 4.5). Whenever possible, alternative medications should be considered, and, if necessary, consider temporarily discontinuing Crestor therapy. In situations where co-administration of these medicinal products with Crestor is unavoidable, the benefit and the risk of concurrent treatment and Crestor dosing adjustments should be carefully considered (see section 4.5).


Crestor is contraindicated: - in patients with hypersensitivity to rosuvastatin or to any of the excipients. - in patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 times the upper limit of normal (ULN). - in patients with severe renal impairment (creatinine clearance <30 ml/min). - in patients with myopathy. - in patients receiving concomitant combination of sofosbuvir/velpatasvir/voxilaprevir (see section 4.5) - in patients receiving concomitant ciclosporin. - during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures. The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include:  moderate renal impairment (creatinine clearance < 60 ml/min)  hypothyroidism  personal or family history of hereditary muscular disorders  previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate  alcohol abuse  situations where an increase in plasma levels may occur  Asian patients  concomitant use of fibrates. (See sections 4.4, 4.5 and 5.2)

Renal Effects

Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of Crestor, in particular 40 mg, where it was transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive renal disease (see section 4.8). The reporting rate for serious renal events in post-marketing use is higher at the 40 mg dose. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40 mg.

Skeletal Muscle Effects

Effects on skeletal muscle e.g. myalgia, myopathy and, rarely, rhabdomyolysis have been reported in Crestor-treated patients with all doses and in particular with doses > 20 mg. Very rare cases of rhabdomyolysis have been reported with the use of ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction cannot be excluded (see section 4.5) and caution should be exercised with their combined use. As with other HMG-CoA reductase inhibitors, the reporting rate for rhabdomyolysis associated with Crestor in post-marketing use is higher at the 40 mg dose.

Creatine Kinase Measurement

Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase which may confound interpretation of the result. If CK levels are significantly elevated at baseline (>5xULN) a confirmatory test should be carried out within 5 – 7 days. If the repeat test confirms a baseline CK >5xULN, treatment should not be started.

Before Treatment

Crestor, as with other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis.

Such factors include:

·        renal impairment

·        hypothyroidism

·        personal or family history of hereditary muscular disorders

·        previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate

·        alcohol abuse

·        age >70 years

·        situations where an increase in plasma levels may occur (see sections 4.2, 4.5 and 5.2)

·        concomitant use of fibrates.

 

In such patients the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended. If CK levels are significantly elevated at baseline (>5xULN) treatment should not be started.

Whilst on Treatment

Patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. CK levels should be measured in these patients. Therapy should be discontinued if CK levels are markedly elevated (>5xULN) or if muscular symptoms are severe and cause daily discomfort (even if CK levels are ≤5xULN). If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing Crestor or an alternative HMG-CoA reductase inhibitor at the lowest dose with close monitoring. Routine monitoring of CK levels in asymptomatic patients is not warranted. There have been very rare reports of an immune-mediated necrotising myopathy (IMNM) during or after treatment with statins, including rosuvastatin. IMNM is clinically characterised by proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment.

 

In few cases, statins have been reported to induce de novo or aggravate pre- existing myasthenia gravis or ocular myasthenia (see section 4.8). Crestor should be discontinued in case of aggravation of symptoms. Recurrences when the same or a different statin was (re-) administered have been reported.

 

In clinical trials, there was no evidence of increased skeletal muscle effects in the small number of patients dosed with Crestor and concomitant therapy.

However, an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives including gemfibrozil, ciclosporin, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when given concomitantly with some HMG-CoA reductase inhibitors. Therefore, the combination of Crestor and gemfibrozil is not recommended. The benefit of further alterations in lipid levels by the combined use of Crestor with fibrates or niacin should be carefully weighed against the potential risks of such combinations. The 40 mg dose is contraindicated with concomitant use of a fibrate (see sections 4.5 and 4.8).

Crestor must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination (see section 4.5). Patients should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness. Statin therapy may be re-introduced seven days after the last dose of fusidic acid. In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g. for the treatment of severe infections, the need for co-administration of Crestor and fusidic acid should only be considered on a case by case basis and under close medical supervision.

 

Crestor should not be used in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).

Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which could be life-threatening or fatal, have been reported with rosuvastatin (see section 4.8). At the time of prescription, patients should be advised of the signs and symptoms of severe skin reactions and be closely monitored. If signs and symptoms suggestive of this reaction appear, Crestor should be discontinued immediately and an alternative treatment should be considered.

 

If the patient has developed a serious reaction such as SJS or DRESS with the use of Crestor, treatment with Crestor must not be restarted in this patient at any time.

 

Liver Effects

As with other HMG-CoA reductase inhibitors, Crestor should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease.

 

It is recommended that liver function tests be carried out prior to, and 3 months following, the initiation of treatment. Crestor should be discontinued or the dose reduced if the level of serum transaminases is greater than 3 times the upper limit of normal. The reporting rate for serious hepatic events (consisting mainly of increased hepatic transaminases) in post-marketing use is higher at the 40 mg dose.

In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with Crestor.

Race

Pharmacokinetic studies show an increase in exposure in Asian subjects compared with Caucasians (see sections 4.2, 4.3 and 5.2).

Protease Inhibitors

Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. Consideration should be given both to the benefit of lipid lowering by use of Crestor in HIV patients receiving protease inhibitors and the potential for increased rosuvastatin plasma concentrations when initiating and up titrating Crestor doses in patients treated with protease inhibitors. The concomitant use with certain protease inhibitors is not recommended unless the dose of Crestor is adjusted. (See sections 4.2 and 4.5).

Lactose Intolerance

 

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

Interstitial Lung Disease

Exceptional cases of interstitial lung disease have been reported with some statins, especially with long-term therapy (see section 4.8). Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.

Diabetes Mellitus

Some evidence suggests that statins as a class raise blood glucose and in some patients, at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5.6 to 6.9 mmol/l, BMI >30 kg/m2, raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.

In the JUPITER study, the reported overall frequency of diabetes mellitus was 2.8% in rosuvastatin and 2.3% in placebo, mostly in patients with fasting glucose 5.6 to 6.9 mmol/l.

Paediatric Population

The evaluation of linear growth (height), weight, BMI (body mass index), and secondary characteristics of sexual maturation by Tanner staging in paediatric patients 7 to 17 years of age taking rosuvastatin is limited to a two-year period. After two years of study treatment, no effect on growth, weight, BMI or sexual maturation was detected (see section 5.1).

 

In a clinical trial of children and adolescents receiving rosuvastatin for

52 weeks, CK elevations >10xULN and muscle symptoms following exercise or increased physical activity were observed more frequently compared to observations in clinical trials in adults (see section 4.8).


Effect of co-administered medicinal products on rosuvastatin

Transporter protein inhibitors: Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter OATP1B1 and efflux transporter BCRP. Concomitant administration of Crestor with medicinal products that are inhibitors of these transporter proteins may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy (see sections 4.2, 4.4 and 4.5 Table 1).

Ciclosporin: During concomitant treatment with Crestor and ciclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers (see Table 1). Crestor is contraindicated in patients receiving

 

concomitant ciclosporin (see section 4.3). Concomitant administration did not affect plasma concentrations of ciclosporin.

Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant protease inhibitor use may strongly increase rosuvastatin exposure (see Table 1). For instance, in a pharmacokinetic study, co-administration of 10 mg rosuvastatin and a combination product of two protease inhibitors

(300 mg atazanavir/100 mg ritonavir) in healthy volunteers was associated with an approximately three-fold and seven-fold increase in rosuvastatin AUC and Cmax respectively. The concomitant use of Crestor and some protease inhibitor combinations may be considered after careful consideration of Crestor dose adjustments based on the expected increase in rosuvastatin exposure (see sections 4.2, 4.4 and 4.5 Table 1).

Gemfibrozil and other lipid-lowering products: Concomitant use of Crestor and gemfibrozil resulted in a 2-fold increase in rosuvastatin Cmax and AUC (see section 4.4).

 

Based on data from specific interaction studies no pharmacokinetic relevant interaction with fenofibrate is expected, however a pharmacodynamic interaction may occur. Gemfibrozil, fenofibrate, other fibrates and lipid lowering doses (> or equal to 1 g/day) of niacin (nicotinic acid) increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. The 40 mg dose is contraindicated with concomitant use of a fibrate (see sections 4.3 and 4.4). These patients should also start with the 5 mg dose.

Ezetimibe: Concomitant use of 10 mg Crestor and 10 mg ezetimibe resulted in a 1.2-fold increase in AUC of rosuvastatin in hypercholesterolaemic subjects (Table 1). A pharmacodynamic interaction, in terms of adverse effects, between Crestor and ezetimibe cannot be ruled out (see section 4.4).

Antacid: The simultaneous dosing of Crestor with an antacid suspension containing aluminium and magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%. This effect was mitigated when the antacid was dosed 2 hours after Crestor. The clinical relevance of this interaction has not been studied.

Erythromycin: Concomitant use of Crestor and erythromycin resulted in a 20% decrease in AUC and a 30% decrease in Cmax of rosuvastatin. This interaction may be caused by the increase in gut motility caused by erythromycin.

Ticagrelor: Ticagrelor might affect renal excretion of rosuvastatin, increasing the risk for rosuvastatin accumulation. Although the exact mechanism is not known, in some cases, concomitant use of ticagrelor and rosuvastatin led to renal function decrease, increased CPK level and rhabdomyolysis.

Cytochrome P450 enzymes: Results from in vitro and in vivo studies show that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450

 

isoenzymes. In addition, rosuvastatin is a poor substrate for these isoenzymes. Therefore, drug interactions resulting from cytochrome P450-mediated metabolism are not expected. No clinically relevant interactions have been observed between rosuvastatin and either fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).

Interactions requiring rosuvastatin dose adjustments (see also Table 1): When it is necessary to co-administer Crestor with other medicinal products known to increase exposure to rosuvastatin, doses of Crestor should be adjusted. Start with a 5 mg once daily dose of Crestor if the expected increase in exposure (AUC) is approximately 2-fold or higher. The maximum daily dose of Crestor should be adjusted so that the expected rosuvastatin exposure would not likely exceed that of a 40 mg daily dose of Crestor taken without interacting medicinal products, for example a 20 mg dose of Crestor with gemfibrozil (1.9-fold increase), and a 10 mg dose of Crestor with combination ritonavir/atazanavir (3.1-fold increase).

If medicinal product is observed to increase rosuvastatin AUC less than 2-fold, the starting dose need not be decreased but caution should be taken if increasing the Crestor dose above 20mg.

 

The following medical product/combinations did not have a clinically significant effect on the AUC ratio of rosuvastatin at coadministration: Aleglitazar 0.3 mg 7 days dosing; Fenofibrate 67 mg 7 days TID dosing; Fluconazole 200mg 11 days OD dosing; Fosamprenavir 700 mg/ritonavir 100 mg 8 days BID dosing; Ketoconazole 200 mg 7 days BID dosing; Rifampin 450 mg 7 days OD dosing; Silymarin 140 mg 5 days TID dosing.

 

Effect of rosuvastatin on co-administered medicinal products

Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, the initiation of treatment or dosage up-titration of Crestor in patients treated concomitantly with vitamin K antagonists (e.g. warfarin or another coumarin anticoagulant) may result in an increase in International Normalised Ratio (INR). Discontinuation or down-titration of Crestor may result in a decrease in INR. In such situations, appropriate monitoring of INR is desirable.

Oral contraceptive/hormone replacement therapy (HRT): Concomitant use of Crestor and an oral contraceptive resulted in an increase in ethinyl estradiol and norgestrel AUC of 26% and 34%, respectively. These increased plasma levels should be considered when selecting oral contraceptive doses. There are no pharmacokinetic data available in subjects taking concomitant Crestor and HRT, therefore, a similar effect cannot be excluded. However, the combination has been extensively used in women in clinical trials and was well tolerated.

Other medicinal products:

Digoxin: Based on data from specific interaction studies no clinically relevant interaction with digoxin is expected.

Fusidic Acid: Interaction studies with rosuvastatin and fusidic acid have not been conducted. The risk of myopathy, including rhabdomyolysis may be increased by the concomitant administration of systemic fusidic acid with statins. The mechanism of this interaction (whether it is pharmacodynamic or pharmacokinetic, or both) is yet unknown. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination.

If treatment with systemic fusidic acid is necessary, Crestor treatment should be discontinued throughout the duration of the fusidic acid treatment. Also see section 4.4.

Paediatric population: Interaction studies have only been performed in adults. The extent of interactions in the paediatric population is not known.

 


Crestor is contraindicated in pregnancy and lactation.

Women of child bearing potential should use appropriate contraceptive measures.

Since cholesterol and other products of cholesterol biosynthesis are essential for the development of the foetus, the potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy. Animal studies provide limited evidence of reproductive toxicity (see section 5.3). If a patient becomes pregnant during use of this product, treatment should be discontinued immediately.

 

Rosuvastatin is excreted in the milk of rats. There are no data with respect to excretion in milk in humans (see section 4.3).


Studies to determine the effect of Crestor on the ability to drive and use machines have not been conducted. However, based on its pharmacodynamic properties, Crestor is unlikely to affect this ability. When driving vehicles or operating machines, it should be taken into account that dizziness may occur during treatment.

 


The adverse reactions seen with Crestor are generally mild and transient. In controlled clinical trials, less than 4% of Crestor-treated patients were withdrawn due to adverse reactions.

Tabulated list of adverse reactions

Based on data from clinical studies and extensive post-marketing experience, the following table presents the adverse reaction profile for rosuvastatin. Adverse reactions listed below are classified according to frequency and system organ class (SOC).

The frequencies of adverse reactions are ranked according to the following convention: Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).

Table 2. Adverse reactions based on data from clinical studies and post-marketing experience

System organ class

Common

Uncommon

Rare

Very rare

Not known

Blood and lymphatic system disorders

 

 

Thrombocytopenia

 

 

Immune system disorders

 

 

Hypersensitivity reactions including angioedema

 

 

Endocrine disorders

Diabetes mellitus1

 

 

 

 

Psychiatric disorders

 

 

 

 

Depression

Nervous

system

Headache

 

 

Polyneuropathy

Peripheral

 

 

System organ class

Common

Uncommon

Rare

Very rare

Not known

disorders

Dizziness

 

 

Memory loss

neuropathy

Sleep disturbances (including insomnia and nightmares)

Myasthenia gravis

Eye disorders

 

 

 

 

Ocular myasthenia

Respiratory, thoracic and mediastinal disorders

 

 

 

 

Cough Dyspnoea

Gastro- intestinal disorders

Constipation Nausea Abdominal pain

 

Pancreatitis

 

Diarrhoea

Hepatobiliary disorders

 

 

Increased hepatic transaminases

Jaundice Hepatitis

 

Skin and subcutaneous tissue disorders

 

Pruritus Rash Urticaria

 

 

Stevens- Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS)

Musculo- skeletal and connective tissue disorders

Myalgia

 

Myopathy (including myositis) Rhabdomyolysis Lupus-like syndrome Muscle rupture

Arthralgia

Tendon disorders, sometimes complicated by rupture

Immune- mediated

necrotising

 

 

System organ class

Common

Uncommon

Rare

Very rare

Not known

 

 

 

 

 

myopathy

Renal and urinary disorders

 

 

 

Haematuria

 

Reproductive system and breast disorders

 

 

 

Gynaecomastia

 

General disorders and administration site conditions

Asthenia

 

 

 

Oedema

1 Frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/L, BMI >30 kg/m2, raised triglycerides, history of hypertension).

As with other HMG-CoA reductase inhibitors, the incidence of adverse drug reactions tends to be dose dependent.

Renal effects: Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with Crestor. Shifts in urine protein from none or trace to ++ or more were seen in <1% of patients at some time during treatment with 10 and 20 mg, and in approximately 3% of patients treated with 40 mg. A minor increase in shift from none or trace to + was observed with the 20 mg dose. In most cases, proteinuria decreases or disappears spontaneously on continued therapy. Review of data from clinical trials and

post-marketing experience to date has not identified a causal association between proteinuria and acute or progressive renal disease.

Haematuria has been observed in patients treated with Crestor and clinical trial data show that the occurrence is low.

Skeletal muscle effects: Effects on skeletal muscle e.g. myalgia, myopathy (including myositis) and, rarely, rhabdomyolysis with and without acute renal failure have been reported in Crestor-treated patients with all doses and in particular with doses > 20 mg.

A dose-related increase in CK levels has been observed in patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient. If CK levels are elevated (>5xULN), treatment should be discontinued (see

section 4.4).

 

Liver effects: As with other HMG-CoA reductase inhibitors, a dose-related increase in transaminases has been observed in a small number of patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient.

 

The following adverse events have been reported with some statins: Sexual dysfunction.

Exceptional cases of interstitial lung disease, especially with long term therapy (see section 4.4).

The reporting rates for rhabdomyolysis, serious renal events and serious hepatic events (consisting mainly of increased hepatic transaminases) is higher at the 40 mg dose.

Paediatric population: Creatine kinase elevations >10xULN and muscle symptoms following exercise or increased physical activity were observed more frequently in a 52-week clinical trial of children and adolescents compared to adults (see section 4.4). In other respects, the safety profile of rosuvastatin was similar in children and adolescents compared to adults.

To report any side effect(s):

·       

·       Saudi Arabia:

 

 

-  The National Pharmacovigilance Centre (NPC)

o   Toll free phone: 19999

o   E-mail: npc.drug@sfda.gov.sa

o   Website: https://ade.sfda.gov.sa/

 
  

·   Other GCC States:

- Please contact the relevant competent authority.


There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Liver function and CK levels should be monitored. Haemodialysis is unlikely to be of benefit.


Pharmacotherapeutic group: HMG-CoA reductase inhibitors

ATC code: C10A A07

Mechanism of action

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering.

Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.

Pharmacodynamic effects

Crestor reduces elevated LDL-cholesterol, total cholesterol and triglycerides and increases HDL-cholesterol. It also lowers ApoB, non-HDL-C, VLDL-C, VLDL- TG and increases ApoA-I (see Table 3). Crestor also lowers the LDL-C/HDL-C, total C/HDL-C and non-HDL-C/HDL-C and the ApoB/ApoA-I ratios.

 

Table 3       Dose response in patients with primary hypercholesterolaemia (type IIa and IIb) (adjusted mean percent change from baseline)

 

Dose

N

LDL-C

Total-C

HDL-C

TG

nonHDL-C

ApoB

ApoA-I

Placebo

13

-7

-5

3

-3

-7

-3

0

5

17

-45

-33

13

-35

-44

-38

4

10

17

-52

-36

14

-10

-48

-42

4

20

17

-55

-40

8

-23

-51

-46

5

40

18

-63

-46

10

-28

-60

-54

0

 

 

A therapeutic effect is obtained within 1 week following treatment initiation and 90% of maximum response is achieved in 2 weeks. The maximum response is usually achieved by 4 weeks and is maintained after that.

Clinical efficacy and safety

Crestor is effective in adults with hypercholesterolaemia, with and without hypertriglyceridaemia, regardless of race, sex or age and in special populations such as diabetics or patients with familial hypercholesterolaemia.

From pooled phase III data, Crestor has been shown to be effective at treating the majority of patients with type IIa and IIb hypercholesterolaemia (mean baseline LDL-C about 4.8 mmol/L) to recognised European Atherosclerosis Society (EAS; 1998) guideline targets; about 80% of patients treated with 10 mg reached the EAS targets for LDL-C levels (<3 mmol/L).

 

In a large study, 435 patients with heterozygous familial hypercholesterolaemia were given Crestor from 20 mg to 80 mg in a force-titration design. All doses showed a beneficial effect on lipid parameters and treatment to target goals.

Following titration to a daily dose of 40 mg (12 weeks of treatment), LDL-C was reduced by 53%. Thirty-three percent (33%) of patients reached EAS guidelines for LDL-C levels (<3 mmol/L).

In a force-titration, open label trial, 42 patients (including 8 paediatric patients) with homozygous familial hypercholesterolaemia were evaluated for their response to Crestor 20 – 40 mg. In the overall population, the mean LDL-C reduction was 22%.

In clinical studies with a limited number of patients, Crestor has been shown to have additive efficacy in lowering triglycerides when used in combination with fenofibrate and in increasing HDL-C levels when used in combination with niacin (see section 4.4).

In a multi-centre, double-blind, placebo-controlled clinical study (METEOR), 984 patients between 45 and 70 years of age and at low risk for coronary heart disease (defined as Framingham risk <10% over 10 years), with a mean LDL-C of 4.0 mmol/L (154.5 mg/dL), but with subclinical atherosclerosis (detected by Carotid Intima Media Thickness) were randomised to 40 mg rosuvastatin once daily or placebo for 2 years. Rosuvastatin significantly slowed the rate of progression of the maximum CIMT for the 12 carotid artery sites compared to placebo by -0.0145 mm/year [95% confidence interval -0.0196, -0.0093; p<0.0001]. The change from baseline was -0.0014 mm/year (-0.12%/year (non- significant)) for rosuvastatin compared to a progression of +0.0131 mm/year (1.12%/year (p<0.0001)) for placebo. No direct correlation between CIMT decrease and reduction of the risk of cardiovascular events has yet been demonstrated. The population studied in METEOR is low risk for coronary heart disease and does not represent the target population of Crestor 40 mg. The

40 mg dose should only be prescribed in patients with severe hypercholesterolaemia at high cardiovascular risk (see section 4.2).

In the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the effect of rosuvastatin on the occurrence of major atherosclerotic cardiovascular disease events was assessed in 17,802 men (≥50 years) and women (≥60 years).

Study participants were randomly assigned to placebo (n=8901) or rosuvastatin 20 mg once daily (n=8901) and were followed for a mean duration of 2 years.

LDL-cholesterol concentration was reduced by 45% (p<0.001) in the rosuvastatin group compared to the placebo group.

In a post-hoc analysis of a high-risk subgroup of subjects with a baseline Framingham risk score >20% (1558 subjects) there was a significant reduction in the combined end-point of cardiovascular death, stroke and myocardial infarction (p=0.028) on rosuvastatin treatment versus placebo. The absolute risk

 

reduction in the event rate per 1000 patient-years was 8.8. Total mortality was unchanged in this high-risk group (p=0.193). In a post-hoc analysis of a high- risk subgroup of subjects (9302 subjects total) with a baseline SCORE risk ≥5% (extrapolated to include subjects above 65 yrs) there was a significant reduction in the combined end-point of cardiovascular death, stroke and myocardial infarction (p=0.0003) on rosuvastatin treatment versus placebo. The absolute risk reduction in the event rate was 5.1 per 1000 patient-years. Total mortality was unchanged in this high-risk group (p=0.076).

In the JUPITER trial, there were 6.6% of rosuvastatin and 6.2% of placebo subjects who discontinued use of study medication due to an adverse event. The most common adverse events that led to treatment discontinuation were: myalgia (0.3% rosuvastatin, 0.2% placebo), abdominal pain (0.03% rosuvastatin, 0.02% placebo) and rash (0.02% rosuvastatin, 0.03% placebo). The most common adverse events at a rate greater than or equal to placebo were urinary tract infection (8.7% rosuvastatin, 8.6% placebo), nasopharyngitis (7.6% rosuvastatin, 7.2% placebo), back pain (7.6% rosuvastatin, 6.9% placebo) and myalgia (7.6% rosuvastatin, 6.6% placebo).

Paediatric population

In a double-blind, randomised, multi-centre, placebo-controlled, 12-week study (n=176, 97 male and 79 female) followed by a 40-week (n=173, 96 male and 77 female), open-label, rosuvastatin dose-titration phase, patients 10 to 17 years of age (Tanner stage II-V, females at least 1-year post-menarche) with heterozygous familial hypercholesterolaemia received rosuvastatin 5, 10 or

20 mg or placebo daily for 12 weeks and then all received rosuvastatin daily for 40 weeks. At study entry, approximately 30% of the patients were 10 to 13 years and approximately 17%, 18%, 40%, and 25% were Tanner stage II, III, IV, and V, respectively.

LDL-C was reduced 38.3%, 44.6%, and 50.0% by rosuvastatin 5, 10 and 20 mg, respectively, compared to 0.7% for placebo.

At the end of the 40-week, open-label, titration to goal, dosing up to a maximum of 20 mg once daily, 70 of 173 patients (40.5%) had achieved the LDL-C goal of less than 2.8 mmol/L.

 

After 52 weeks of study treatment, no effect on growth, weight, BMI or sexual maturation was detected (see section 4.4). This trial (n=176) was not suited for comparison of rare adverse drug events.

Rosuvastatin was also studied in a 2-year open-label, titration-to-goal study in

198 children with heterozygous familial hypercholesterolaemia aged 6 to 17 years (88 male and 110 female, Tanner stage <II-V). The starting dose for all patients was 5 mg rosuvastatin once daily. Patients aged 7 to 9 years (n=64) could titrate to a maximum dose of 10 mg once daily and patients aged 10 to 17 years (n=134) to a maximum dose of 20 mg once daily.

 

After 24 months of treatment with rosuvastatin, the LS mean percent reduction from the baseline value in LDL-C was -43% (Baseline: 236 mg/dL, Month 24: 133 mg/dL). For each age group, the LS mean percent reductions from baseline values in LDL-C were -43% (Baseline: 234 mg/dL, Month 24: 124 mg/dL),

-45% (Baseline: 234 mg/dL, Month 24: 124 mg/dL) and -35% (Baseline:

241 mg/dL, Month 24: 153 mg/dL) in the 7 to <10, 10 to <14, and 14 to <18 age groups, respectively.

Rosuvastatin 5 mg, 10 mg, and 20 mg also achieved statistically significant mean changes from baseline for the following secondary lipid and lipoprotein variables: HDL-C, TC, non-HDL-C, LDL-C/HDL-C, TC/HDL-C, TG/HDL-C,

non-HDL C/HDL-C, ApoB, ApoB/ApoA-1. These changes were each in the direction of improved lipid responses and were sustained over 2 years.

No effect on growth, weight, BMI or sexual maturation was detected after 24 months of treatment (see section 4.4).

Rosuvastatin was studied in a randomised, double-blind, placebo-controlled, multi-centre, cross-over study with 20 mg once daily versus placebo in 14 children and adolescents (aged from 7 to 17 years) with homozygous familial hypercholesterolaemia. The study included an active 4-week dietary lead-in phase during which patients were treated with rosuvastatin 10 mg, a cross-over phase that consisted of a 6-week treatment period with rosuvastatin 20 mg preceded or followed by a 6-week placebo treatment period, and a 12-week maintenance phase during which all patients were treated with rosuvastatin

20 mg. Patients who entered the study on ezetimibe or apheresis therapy continued the treatment throughout the entire study.

A statistically significant (p=0.005) reduction in LDL-C (22.3%, 85.4 mg/dL or 2.2 mmol/L) was observed following 6 weeks of treatment with rosuvastatin

20 mg versus placebo. Statistically significant reductions in Total-C (20.1%, p=0.003), non-HDL-C (22.9%, p=0.003) and ApoB (17.1%, p=0.024) were

observed. Reductions were also seen in TG, LDL-C/HDL-C, Total-C/HDL-C, non-HDL-C/HDL-C and ApoB/ApoA-1 following 6 weeks of treatment with rosuvastatin 20 mg versus placebo. The reduction in LDL-C after 6 weeks of treatment with rosuvastatin 20 mg following 6 weeks of treatment with placebo was maintained over 12 weeks of continuous therapy. One patient had a further reduction in LDL-C (8.0%), Total-C (6.7%) and non-HDL-C (7.4%) following 6 weeks of treatment with 40 mg after up-titration.

During an extended open-label treatment in 9 of these patients with 20 mg rosuvastatin for up to 90 weeks, the LDL-C reduction was maintained in the range of -12.1% to -21.3%.

In the 7 evaluable children and adolescent patients (aged from 8 to 17 years) from the force-titration open label study with homozygous familial hypercholesterolaemia (see above), the percent reduction in LDL-C (21.0%), Total-C (19.2%) and non-HDL-C (21.0%) from baseline following 6 weeks of treatment with rosuvastatin 20 mg was consistent with that observed in the

 

aforementioned study in children and adolescents with homozygous familial hypercholesterolaemia.

The European Medicines Agency has waived the obligation to submit the results of studies with rosuvastatin in all subsets of the paediatric population in the treatment of homozygous familial hypercholesterolaemia, primary combined (mixed) dyslipidaemia and in the prevention of cardiovascular events (see section 4.2 for information on paediatric use).

 


Absorption: Maximum rosuvastatin plasma concentrations are achieved approximately 5 hours after oral administration. The absolute bioavailability is approximately 20%.

Distribution: Rosuvastatin is taken up extensively by the liver which is the primary site of cholesterol synthesis and LDL-C clearance. The volume of distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly to albumin.

Metabolism: Rosuvastatin undergoes limited metabolism (approximately 10%). In vitro metabolism studies using human hepatocytes indicate that rosuvastatin is a poor substrate for cytochrome P450-based metabolism. CYP2C9 was the principal isoenzyme involved, with 2C19, 3A4 and 2D6 involved to a lesser extent. The main metabolites identified are the N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin whereas the lactone form is considered clinically inactive.

Rosuvastatin accounts for greater than 90% of the circulating HMG-CoA reductase inhibitor activity.

Excretion: Approximately 90% of the rosuvastatin dose is excreted unchanged in the faeces (consisting of absorbed and non-absorbed active substance) and the remaining part is excreted in urine. Approximately 5% is excreted unchanged in urine. The plasma elimination half-life is approximately 19 hours. The elimination half-life does not increase at higher doses. The geometric mean plasma clearance is approximately 50 litres/hour (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, the hepatic uptake of rosuvastatin involves the membrane transporter OATP-C. This transporter is important in the hepatic elimination of rosuvastatin.

Linearity: Systemic exposure of rosuvastatin increases in proportion to dose. There are no changes in pharmacokinetic parameters following multiple daily doses.

Special populations:

Age and sex: There was no clinically relevant effect of age or sex on the pharmacokinetics of rosuvastatin in adults. The exposure in children and adolescents with heterozygous familial hypercholesterolemia appears to be

 

similar to or lower than that in adult patients with dyslipidaemia (see “Paediatric population” below).

Race: Pharmacokinetic studies show an approximate 2-fold elevation in median AUC and Cmax in Asian subjects (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared with Caucasians; Asian-Indians show an approximate 1.3- fold elevation in median AUC and Cmax. A population pharmacokinetic analysis revealed no clinically relevant differences in pharmacokinetics between Caucasian and Black groups.

Renal insufficiency: In a study in subjects with varying degrees of renal impairment, mild to moderate renal disease had no influence on plasma concentration of rosuvastatin or the N-desmethyl metabolite. Subjects with severe impairment (CrCl <30 ml/min) had a 3-fold increase in plasma concentration and a 9-fold increase in the N-desmethyl metabolite concentration compared to healthy volunteers. Steady-state plasma concentrations of rosuvastatin in subjects undergoing haemodialysis were approximately 50% greater compared to healthy volunteers.

Hepatic insufficiency: In a study with subjects with varying degrees of hepatic impairment, there was no evidence of increased exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below. However, two subjects with Child-Pugh scores of 8 and 9 showed an increase in systemic exposure of at least 2-fold compared to subjects with lower Child-Pugh scores. There is no experience in subjects with Child-Pugh scores above 9.

Genetic polymorphisms: Disposition of HMG-CoA reductase inhibitors, including rosuvastatin, involves OATP1B1 and BCRP transporter proteins. In patients with SLCO1B1 (OATP1B1) and/or ABCG2 (BCRP) genetic polymorphisms there is a risk of increased rosuvastatin exposure. Individual polymorphisms of SLCO1B1 c.521CC and ABCG2 c.421AA are associated with a higher rosuvastatin exposure (AUC) compared to the SLCO1B1 c.521TT or ABCG2 c.421CC genotypes. This specific genotyping is not established in clinical practice, but for patients who are known to have these types of polymorphisms, a lower daily dose of Crestor is recommended.

Paediatric population: Two pharmacokinetic studies with rosuvastatin (given as tablets) in paediatric patients with heterozygous familial hypercholesterolaemia 10 to 17 or 6 to 17 years of age (total of 214 patients) demonstrated that exposure in paediatric patients appears comparable to or lower than that in adult patients. Rosuvastatin exposure was predictable with respect to dose and time over a 2-year period.


Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity and carcinogenicity potential. Specific tests for effects on hERG have not been evaluated. Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to clinical exposure levels were as follows: In repeated-dose toxicity studies

 

histopathologic liver changes likely due to the pharmacologic action of rosuvastatin were observed in mouse, rat, and to a lesser extent with effects in the gall bladder in dogs, but not in monkeys. In addition, testicular toxicity was observed in monkeys and dogs at higher dosages. Reproductive toxicity was evident in rats, with reduced litter sizes, litter weight and pup survival observed at maternally toxic doses, where systemic exposures were several times above the therapeutic exposure level.


Tablet core

Lactose monohydrate

Microcrystalline cellulose

Calcium phosphate

Crospovidone

Magnesium stearate

 

Tablet coat

Lactose monohydrate Hypromellose Triacetin

Titanium dioxide (E171)

Ferric oxide, yellow (E172) (5 mg tablet)

Ferric oxide, red (E172) (10 mg, 20 mg and 40 mg tablets)


Not applicable.


3 years.

Blisters: Store below 30°C. Store in the original package in order to protect from moisture.

HDPE containers: Store below 30°C. Keep bottle tightly closed in order to protect from moisture.


5 mg, 10 mg, 20 mg and 40 mg:

Blisters of aluminium laminate/aluminium foil of 7, 14, 15, 20, 28, 30, 42, 50,

56, 60, 84, 90, 98 and 100 tablets

HDPE containers: 30 and 100 tablets. Not all pack sizes may be marketed.


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


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July 2023
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