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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)

Your doctor has given you Aranesp (an anti‑anaemic) to treat your anaemia. Anaemia is when your blood does not contain enough red blood cells and the symptoms may be fatigue, weakness and shortness of breath.

 

Aranesp works in exactly the same way as the natural hormone erythropoietin. Erythropoietin is produced in your kidneys and encourages your bone marrow to produce more red blood cells. The active substance of Aranesp is darbepoetin alfa produced by gene‑technology in Chinese Hamster Ovary Cells (CHO‑K1).

 

If you have chronic renal failure

 

Aranesp is used to treat symptomatic anaemia that is associated with chronic renal failure (kidney failure) in adults and children. In kidney failure, the kidney does not produce enough of the natural hormone erythropoietin which can often cause anaemia.

 

Because it will take your body some time to make more red blood cells, it will be about four weeks before you notice any effect. Your normal dialysis routine will not affect the ability of Aranesp to treat your anaemia.

 

If you are receiving chemotherapy

 

Aranesp is used to treat symptomatic anaemia in adult cancer patients with non‑bone marrow cancers (non‑myeloid malignancies) who are receiving chemotherapy.

 

One of the main side effects of chemotherapy is that it stops the bone marrow producing enough blood cells. Towards the end of your chemotherapy course, particularly if you have had a lot of chemotherapy, your red blood cell count may fall making you anaemic.


Do not use Aranesp:

 

-              if you are allergic to darbepoetin alfa or any of the other ingredients of this medicine (listed in section 6).

-              if you have been diagnosed with high blood pressure which is not being controlled with other medicines prescribed by your doctor.

 

Warnings and precautions

 

Talk to your doctor, pharmacist or nurse before using Aranesp.

 

Please tell your doctor if you are suffering or have suffered from:

-              high blood pressure which is being controlled with medicines prescribed by your doctor;

-              sickle cell anaemia;

-              epileptic fits (seizures);

-              convulsions (fits or seizures);

-              liver disease;

-              significant lack of response to medicines used to treat anaemia;

-              an allergy to latex (the needle cap on the pre‑filled syringe contains a derivative of latex); or

-              hepatitis C.

 

Special warnings:

 

 

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOUR PROGRESSION OR RECURRENCE

 

Chronic Renal Failure:

·              In controlled trials, patients experienced greater risks for death, serious cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a haemoglobin level of greater than 11 g/dL.

·              No trial has identified a haemoglobin target level, Aranesp dose, or dosing strategy that does not increase these risks.

·              Use the lowest Aranesp dose sufficient to reduce the need for red blood cell (RBC) transfusions.

 

Cancer:

·              ESAs shortened overall survival and/or increased the risk of tumour progression or recurrence in clinical studies of patients with breast, non‑small cell lung, head and neck, lymphoid, and cervical cancers.

·              Use the lowest dose to avoid red blood cell transfusions.

·              Use ESAs only for anaemia from myelosuppressive chemotherapy.

·              ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure.

·              Discontinue following the completion of a chemotherapy course.

 

 

-              If you have symptoms which include unusual tiredness and a lack of energy this could mean you have pure red cell aplasia (PRCA), which has been reported in patients. PRCA means that the body has stopped or reduced the production of red blood cells which causes severe anaemia. If you experience these symptoms you should contact your doctor who will determine the best course of action to treat your anaemia.

 

-              Take special care with other products that stimulate red blood cell production: Aranesp is one of a group of products that stimulate the production of red blood cells like the human protein erythropoietin does. Your healthcare professional should always record the exact product you are using.

 

-              If you are a patient with chronic renal failure, and particularly if you do not respond properly to Aranesp, your doctor will check your dose of Aranesp because repeatedly increasing your dose of Aranesp if you are not responding to treatment may increase the risk of having a problem of the heart or the blood vessels and could increase risk of myocardial infarction, stroke and death.

 

-              Your doctor should try to keep your haemoglobin level within the appropriate range (see section 3). Your doctor will check that your haemoglobin does not exceed a certain level, as high haemoglobin concentrations could put you at risk of having a problem of the heart or the blood vessels and could increase risk of myocardial infarction, stroke and death.

 

o      Patients with chronic renal failure experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target a haemoglobin level of greater than 11 g/dL in clinical studies. Patients with chronic renal failure and an insufficient haemoglobin response to ESA therapy may be at even greater risk for cardiovascular events and mortality than other patients. Aranesp and other ESAs increased the risks for death and serious cardiovascular events in controlled clinical trials of patients with cancer. These events included myocardial infarction, stroke, congestive heart failure, and haemodialysis vascular access thrombosis. A rate of haemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks.

 

-              If you have symptoms which include severe headache, drowsiness, confusion, problems with your eyesight, nausea, vomiting or fits (seizures), it could mean that you have very high blood pressure. If you experience these symptoms you should contact your doctor.

 

-              If you are a cancer patient you should be aware that Aranesp may act as a blood cell growth factor and in some circumstances may have a negative impact on your cancer. Depending on your individual situation a blood transfusion may be preferable. Please discuss this with your doctor.

 

o      Erythropoiesis-stimulating agents, when administered to target a haemoglobin of > 12 g/dL, shortened the time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy. ESAs also shortened survival in patients with metastatic breast cancer and in patients with lymphoid malignancy receiving chemotherapy when administered to target a haemoglobin of ≥ 12 g/dL. In addition, ESAs shortened survival in patients with non-small cell lung cancer and in a study enrolling patients with various malignancies who were not receiving chemotherapy or radiotherapy; in these two studies, ESAs were administered to target a haemoglobin of ≥ 12 g/dL. Although studies evaluated haemoglobin targets of ≥ 12 g/dL in these tumour types, the risk of shortened survival and tumour progression have not been excluded when ESAs are dosed to target a haemoglobin of < 12 g/dL.

 

-              Misuse by healthy people can cause life‑threatening problems with the heart or blood vessels.

 

-              Serious skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in association with epoetin treatment. SJS/TEN can appear initially as reddish target-like spots or circular patches often with central blisters on the trunk. Also, ulcers of mouth, throat, nose, genitals and eyes (red and swollen eyes) can occur. These serious skin rashes are often preceded by fever and/or flu-like symptoms. The rashes may progress to widespread peeling of the skin and life-threatening complications.

If you develop a serious rash or another of these skin symptoms, stop taking Aranesp and contact your doctor or seek medical attention immediately.

 

Other medicines and Aranesp

 

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

 

Cyclosporin and tacrolimus (medicines which suppress the immune system) may be affected by the number of red cells in your blood. It is important to tell your doctor if you are taking either of these medicines.

 

Using Aranesp with food and drink

 

Food and drink do not affect Aranesp.

 

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 or pharmacist for advice before taking this medicine.

 

Aranesp has not been tested in pregnant women. It is important to tell your doctor if you:

·             are pregnant;

·             think you may be pregnant; or

·             plan to get pregnant.

 

It is not known whether darbepoetin alfa is excreted in human milk. You must stop breast‑feeding if you use Aranesp.

 

Driving and using machines

 

Aranesp should not affect your ability to drive or use machinery.

 

Aranesp contains sodium

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium‑free’.

 


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

 

Injecting Aranesp yourself

 

Your doctor may decide that it is best for you, a nurse or a carer to inject Aranesp. Your doctor, nurse or pharmacist will show you how to inject yourself with the pre‑filled syringe. Do not try to inject yourself if you have not been trained. Never inject Aranesp into a vein yourself.

 

If you have chronic renal failure

 

Following blood tests, your doctor has decided you need Aranesp as your haemoglobin level is 10 g/dL or less. Your doctor will tell you how much and how often you must take Aranesp in order to maintain a haemoglobin level between 10 and 11 g/dL. This may vary depending on whether you are an adult or a child.

 

For all adult and paediatric patients ≥ 1 year of age with chronic renal failure, Aranesp is given as a single injection, either under your skin (subcutaneous) or into a vein (intravenous).

 

In order to correct your anaemia, your initial dose of Aranesp per kilogram of your body weight will be either:

·             0.75 micrograms once every two weeks, or

·             0.45 micrograms once weekly.

 

For adult patients not on dialysis, 1.5 micrograms/kg once monthly may also be used as the initial dose.

 

For all adult and paediatric patients ≥ 1 year of age with chronic renal failure, once your anaemia is corrected you will continue to receive Aranesp given as a single injection, either once a week or once every two weeks. For all adults and paediatric patients ≥ 11 years of age not on dialysis, Aranesp could also be given as an injection once monthly.

 

Your doctor will take regular blood samples to measure how your anaemia is responding and may adjust your dose once every four weeks as necessary in order to maintain long term control of your anaemia.

 

Once your anaemia is corrected, your doctor will continue to regularly check your blood and your dose may be adjusted further in order to maintain long term control of your anaemia. Your doctor will inform you if your dose changes.

 

Your doctor will use the lowest effective dose to control the symptoms of your anaemia.

 

If you do not respond adequately to Aranesp, your doctor will check your dose and will inform you if you need to change doses of Aranesp.

 

Your blood pressure will also be checked regularly, particularly at the beginning of your treatment.

 

In some cases, your doctor may recommend that you take iron supplements.

 

Your doctor may decide to change the way that your injection is given (either under the skin or into a vein). If this changes, you will start on the same dose as you have been receiving and your doctor will take blood samples to make sure that your anaemia is still being managed correctly.

 

If your doctor has decided to change your treatment from r‑HuEPO (erythropoietin produced by gene‑technology) to Aranesp, they will choose whether you should receive your Aranesp injection once weekly or once every two weeks. The route of injection is the same as with r‑HuEPO but your doctor will tell you how much you should take, and when, and may adjust your dose if necessary.

 

If you are receiving chemotherapy

 

Following blood tests, your doctor has decided you need Aranesp as your haemoglobin level is 10 g/dL or less. Your doctor will tell you how much and how often you must take Aranesp in order to maintain a haemoglobin level between 10 and 12 g/dL.

 

Aranesp is given as a single injection, either once a week or once every three weeks, under your skin.

 

In order to correct your anaemia, your initial dose will be:

·             500 micrograms once every three weeks (6.75 micrograms of Aranesp per kilogram of your body weight), or

·             2.25 micrograms (once weekly) of Aranesp per kilogram of your body weight.

 

Your doctor will take regular blood samples to measure how your anaemia is responding and may adjust your dose as necessary. Your treatment will continue until approximately four weeks after the end of your chemotherapy. Your doctor will tell you exactly when to stop taking Aranesp.

 

In some cases, your doctor may recommend that you take iron supplements.

 

If you use more Aranesp than you should

 

You could have serious problems if you use more Aranesp than you need, such as very high blood pressure. You should contact your doctor, nurse or pharmacist if this does happen. If you feel unwell in any way you should contact your doctor, nurse or pharmacist immediately.

 

If you forget to use Aranesp

 

Do not use a double dose to make up for a forgotten dose.

 

If you have forgotten a dose of Aranesp, you should contact your doctor to discuss when you should inject the next dose.

 

If you stop using Aranesp

 

If you want to stop using Aranesp, you should discuss it with your doctor first.

 

 


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

 

The following side effects have been experienced by some patients taking Aranesp:

 

Chronic renal failure patients

 

Very common: may affect more than 1 in 10 people

·             High blood pressure (hypertension)

·             Allergic reactions

 

Common: may affect up to 1 in 10 people

·             Stroke

·             Pain around the area injected

·             Rash and/or redness of the skin

 

Uncommon: may affect up to 1 in 100 people

·             Blood clots (thrombosis)

·             Convulsions (fits and seizures)

·             Bruising and bleeding at the site of injection

·             Blood clots in a dialysis access

 

Not known: frequency cannot be estimated from available data

·             Pure red cell aplasia (PRCA) – (anaemia, unusual tiredness, lack of energy)

 

Cancer patients

 

Very common: may affect more than 1 in 10 people

·             Allergic reactions

 

Common: may affect up to 1 in 10 people

·             High blood pressure (hypertension)

·             Blood clots (thrombosis)

·             Pain around the area injected

·             Rash and/or redness of the skin

·             Fluid retention (oedema)

 

Uncommon: may affect up to 1 in 100 people

·             Convulsions (fits and seizures)

·             Bruising and bleeding at the site of injection

 

All patients

 

Not known: frequency cannot be estimated from available data

·             Serious allergic reactions which may include:

·              Sudden life‑threatening allergic reactions (anaphylaxis)

·              Swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing (angioedema)

·              Shortness of breath (allergic bronchospasm)

·              Skin rash

·              Hives (urticaria)

·             Serious skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in association with epoetin treatment. These can appear as reddish target-like macules or circular patches often with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes and can be preceded by fever and flu-like symptoms.

Stop using Aranesp if you develop these symptoms and contact your doctor or seek medical attention immediately. See also section 2.

 

Reporting of side effects

 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to your doctor, pharmacist or nurse. 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.

 

Do not use this medicine after the expiry date which is stated on the carton and on the pre‑filled syringe label after EXP. The expiry date refers to the last day of that month.

 

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not use Aranesp if you think it has been frozen.

 

Keep the pre‑filled syringe in the outer carton in order to protect from light.

 

For the purpose of ambulatory use, Aranesp may be removed from storage once for a maximum single period of seven days at room temperature (up to 25°C). Once a syringe has been removed from the refrigerator and has reached room temperature (up to 25°C) it must either be used within 7 days or disposed of.

 

Do not use this medicine if you notice the pre‑filled syringe contents are cloudy or there are particles in it.

 

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.

 


What Aranesp contains

 

-              The active substance is darbepoetin alfa, r‑HuEPO (erythropoietin produced by gene‑technology). The pre‑filled syringe contains either 10, 20, 30, 40, 50, 60, 80, 100, 150, 300 or 500 micrograms of darbepoetin alfa.

-        The other ingredients: Each 1 mL contains polysorbate 80 (0.05 mg), sodium phosphate monobasic monohydrate (2.12 mg), sodium phosphate dibasic anhydrous (0.66 mg), sodium chloride (8.18 mg) in water for injection, USP (up to 1 mL).

 


What Aranesp looks like and contents of the pack Aranesp is a clear, colourless or slightly pearly solution for injection in a pre-filled syringe. Aranesp pre-filled syringe is available in packs of 1 or 4 pre-filled syringes in a blister wrapping. Not all pack sizes may be marketed.

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

The Netherlands

 

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


This leaflet was last revised in November 2019.
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

وصف لك طبيبك أرانسب (دواء مضاد لفقر الدم) لعلاج فقر الدم لديك. ويقصد بفقر الدم عدم وجود عدد كاف من خلايا الدم الحمراء في الدم، ومن أعراض هذا المرض التعب والضعف وضيق التنفس.

 

يعمل أرانسب بنفس طريقة هرمون الإريثروبويتين الذي يفرز في الجسم بصورة طبيعية. وتنتج الكلى هذا الهرمون، الذي يساعد النخاع العظمي على تكوين المزيد من خلايا الدم الحمراء. إن المادة الفعالة الموجودة بدواء أرانسب هي داربيبويتين الفا والتي يتم إنتاجها باستخدام التكنولوجيا الجينية في خلايا مبيض حيوان أنثى الهامستر الصيني (CHO-K1).

 

إذا كنت تعاني من فشل كلوي مزمن

 

يستخدم أرانسب لعلاج أعراض فقر الدم المصاحبة للفشل الكلوي المزمن لدى البالغين والأطفال. وفي حالة الفشل الكلوي، تعجز الكلى عن إنتاج ما يكفي من هرمون الإريثروبويتين الطبيعي، وغالبا ما يتسبب هذا في الإصابة بفقر الدم.

 

لأن الجسم يستغرق بعض الوقت لتكوين المزيد من خلايا الدم الحمراء، فلن تلحظ أي تأثير للدواء قبل مرور أربعة أسابيع. ولن تؤثر عملية غسيل الكلى الروتينية على قدرة أرانسب على علاج فقر الدم لديك.

 

إذا كنت تتلقى علاجا كيميائيا

 

يستخدم دواء أرانسب في علاج فقر الدم العرضي (الناتج عن مرض آخر)، وذلك لدى مرضى السرطان البالغين الذين لا يعانون من سرطان النخاع العظمي ويتلقون علاجا كيميائيا (ما عدا المرضى المصابين بسرطان النخاع العظمي).

 

إن أحد الآثار الجانبية الرئيسية للعلاج الكيماوي توقف النخاع العظمي عن إنتاج ما يكفي من كريات الدم الحمراء. وفي نهاية دورة العلاج الكيميائي، على الأخص إذا تلقيت نصيبا كبيرا من هذا العلاج، فقد ينخفض تعداد خلايا الدم الحمراء فتصاب بفقر الدم.

 

لا تستخدم أرانسب في الحالات الآتية:

 

-              إذا كانت لديك حساسية من داربيبويتين الفا أو من أي من المكونات الأخرى في هذا الدواء (مدرجة في القسم ٦).

-              إذا كنت تعاني من ارتفاع في ضغط الدم الذي لا يمكن التحكم فيه باستخدام الأدوية التي يصفها لك الطبيب.

 

التحذیرات والاحتیاطات

 

يرجى إخبار طبيبك أو الصيدلي أو الممرض(ة) قبل استخدام أرانسب.

 

يرجى إخبار طبيبك إن كنت تعاني أو سبق لك التعرض لأي مما يلي:

-              ضغط الدم المرتفع والذي يمكن التحكم فيه باستخدام الأدوية التي وصفها لك طبيبك؛

-              فقر دم الخلايا المنجلية؛

-              نوبات الصرع؛

-              تشنجات (نوبات أو صرع)؛

-              أمراض الكبد؛

-              قلة الاستجابة إلى حد بالغ للأدوية المستخدمة في علاج فقر الدم؛

-              حساسية من مادة اللاتكس (غطاء الإبرة الموضوع فوق الحقنة المملوءة مسبقا يحتوي على مشتقات مادة اللاتكس)؛ أو

-              فيروس الكبد الوبائي سي.

 

تحذيرات خاصة:

 

 

تحذيرات: تؤدي الأدوية التي تحفز على تكون خلايا الدم الحمراء (ESAs) إلى زيادة خطر الإصابة بحالات وفاة، احتشاء عضلة القلب، السكتة الدماغية، الجلطات الدموية الوريدية، تخثر الأوعية الدموية، وزيادة تطور أو تكرار حدوث أورام

 

الفشل الكلوي المزمن:

·              في الدراسات الخاضعة للرقابة، تعرض المرضى لمخاطر أكبر للوفاة، وردود فعل خطيرة على القلب والأوعية الدموية، والسكتة الدماغية عند تناولهم الأدوية التي تحفز على تكون خلايا الدم الحمراء (ESAs) لاستهداف مستوى هيموجلوبين أكبر من ١١ جم/ديسيلتر.

·              لم تحدد أي دراسات سريرية مستوى الهيموجلوبين المستهدف، جرعة ارانسب، أو استراتيجية الجرعات التي لا تزيد من هذه المخاطر.

·              استخدم أقل جرعة لتجنب اللجوء لنقل خلايا الدم الحمراء.

 

السرطان:

·              تؤدي الأدوية التي تحفز على تكون خلايا الدم الحمراء (ESAs) إلى تقصير إجمالي لمدة البقاء على قيد الحياة أو إلى زيادة مخاطر تطور أو تكرار الإصابة بالأورام وذلك في بعض الدراسات السريرية لمرضى سرطان الثدي، سرطان الرئة ذو الخلايا غير الصغيرة، سرطان الرأس والرقبة، سرطان الأوعية الليمفاوية، وسرطان عنق الرحم.

·              استخدم أقل جرعة لتجنب اللجوء لنقل خلايا الدم الحمراء.

·              استخدم الأدوية التي تحفز على تكون خلايا الدم الحمراء (ESAs) فقط لعلاج الأنيميا الناجمة عن العلاج الكيماوي المثبط للنخاع العظمي.

·              لا ينصح باستخدام الأدوية التي تحفز على تكون خلايا الدم الحمراء (ESAs) لدى المرضى الذين يتلقون العلاج الكيماوي المثبط للنخاع العظمي في حال أن الغرض من العلاج هو الشفاء.

·              أوقف الدواء عقب الانتهاء من أي دورة علاج كيماوي.

 

 

-              إذا كانت لديك أعراض مثل الشعور بالإرهاق غير المعتاد وفقدان النشاط فيحتمل إصابتك بنوع من فقر الدم يسمى "عدم تنسج الكريات الحمراء النقي" (PRCA) والذي تم تسجيل إصابة بعض المرضى به. ويقصد بهذا النوع من فقر الدم (PRCA) حدوث توقف أو نقص في إنتاج خلايا الدم الحمراء وهذا ما يسبب فقر دم حاد. إذا شعرت بأي من تلك الأعراض فعليك الاتصال بطبيبك المعالج والذي سيحدد لك أفضل خطة علاجية لعلاج فقر الدم.

 

-              اهتم بشكل خاص بأي منتجات أخرى تحفز على تكون خلايا الدم الحمراء ويعتبر أرانسب أحد المنتجات التي تحفز على تكون خلايا الدم الحمراء بنفس الكيفية التي يؤديها البروتين البشري إريثروبويتين. ويجب على مسؤول الرعاية الصحية الخاص بك تسجيل المنتج الذي تستخدمه.

 

-              إذا كنت تعاني من فشل كلوي مزمن، وخاصة إذا كنت لا تستجيب كما ينبغي لأرانسب، فسوف يتحقق طبيبك من الجرعة اللازمة من أرانسب لأن زيادة جرعة أرانسب بشكل متكرر إذا كنت لا تستجيب للعلاج قد تزيد من خطر حدوث مشكلة بالقلب أو الأوعية الدموية ويمكن أن يزيد من خطر احتشاء عضلة القلب والسكتة الدماغية والموت.

 

-              يجب على طبيبك مراعاة الحفاظ على مستوى الهيموجلوبين ضمن النطاق المناسب (انظر القسم ٣). سيتأكد طبيبك أن الهيموجلوبين لا يزيد عن مستوى معين، حيث قد يعرضك زيادة تركيز الهيموجلوبين إلى الإصابة بمشاكل بالقلب أو الأوعية الدموية وزيادة احتشاء عضلة القلب والسكتة الدماغية والوفاة.

 

o            تعرض مرضى الفشل الكلوي المزمن إلى مخاطر اكبر للوفاة واعراض خطيرة في القلب والأوعية الدموية نتيجة تناول الأدوية التي تحفز إنتاج خلايا الدم الحمراء (ESAs) لاستهداف مستوى هيموجلوبين أكبر من ١١ جم/ديسيلتر في الدراسات السريرية. وقد يتعرض مرضى الالتهاب الكلوي المزمن والمرضى الذين يعانون من قلة رد فعل الهيموجلوبين للعلاج بالأدوية التي تحفز على إنتاج خلايا الدم الحمراء (ESAs‏)، إلى زيادة مخاطر الإصابة بأمراض القلب والأوعية الدموية والوفاة أكثر من أي مرضى آخرين. يؤدي أرانسب وأدوية أخرى تحفز على إنتاج خلايا الدم الحمراء (ESAs) إلى زيادة مخاطر الإصابة بحالات وفاة أو ردود فعل القلب والأوعية الدموية الخطيرة وذلك خلال التجارب السريرية المراقبة لدى مرضى السرطان. ومن بين تلك ردود الفعل احتشاء عضلة القلب، السكتة الدماغية، فشل القلب الاحتقاني، و تخثر الأوعية الدموية الناجم عن عمليات الغسيل الكلوي. وقد يساهم زيادة معدل الهيموجلوبين بأكثر من ١ جم/ديسيلتر على مدى أسبوعين في التعرض لتلك المخاطر.

 

-              إذا كنت تعاني من أعراض صداع شديد، وخمول، وارتباك، ومشاكل في النظر، وقيء أو تشنجات (نوبات)، فإن ذلك قد يعني إصابتك بارتفاع ضغط الدم إذا واجهت تلك الأعراض فيجب عليك استشارة طبيبك.

 

-              إن كنت مصابا بالسرطان، فيجب أن تعلم أن أرانسب قد يكون عاملا يؤدي إلى زيادة نمو خلايا الدم وفي بعض الظروف يمكن أن يتسبب في تأثير سلبي على مرض السرطان لديك. وبناء على حالتك الصحية فقد يفضل في هذه الحالة إجراء نقل دم لديك. فيرجى مناقشة الأمر مع طبيبك المعالج.

 

o            أدى تناول الأدوية التي تحفز على إنتاج خلايا الدم الحمراء (ESAs) للوصول إلى معدلات الهيموجلوبين إلى أكثر من ١٢جم/ديسيلتر، إلى تقصير الوقت اللازم لتطور الورم لدى مرضى سرطان الرأس والرقبة المتقدم الذين يتلقوا علاج بالإشعاع. كما أدى إلى تقصير مدة البقاء على قيد الحياة لدى مرضى سرطان الثدي النقيلي ومرضى الورم الليمفاوي الخبيث عند تناولهم تلك الأدوية للوصول إلى معدل ≥ ١٢ جم/ ديسيلتر. علاوة على ذلك، إن تناول الأدوية التي تحفز على إنتاج خلايا الدم الحمراء (ESAs) قد يؤدي إلى تقصير مدة البقاء على قيد الحياة لدى مرضى سرطان الرئة ذو الخلايا غير الصغيرة وفي دراسة على مرضى مختلف أنواع الأورام الخبيثة الذين لا يتلقون علاج كيماوي أو إشعاعي؛ في تلك الدراستين، استمر تناول الأدوية التي تحفز على إنتاج خلايا الدم الحمراء للوصول الى معدل هيموجلوبين يبلغ ≥ ١٢ جم/ ديسيلتر. وعلى الرغم من تقييم الدراستين للوصول إلى معدلات الهيموجلوبين إلى ≥ ١٢ جم/ديسيلتر فى هذه الأنواع من الأورام فلم يستبعد حدوث تقصير مدة البقاء على قيد الحياة وتقدم الورم عند تناول الأدوية التي تحفز على إنتاج خلايا الدم الحمراء (ESAs) للوصول إلى معدل هيموجلوبين يبلغ أقل من ١٢ جم/ ديسيلتر.

 

-              يمكن أن يتسبب سوء استخدام هذا الدواء، من قبل أفراد بصحة جيدة، في حدوث مشاكل خطيرة بالقلب أو الأوعية الدموية.

 

-              تم الإبلاغ عن ردود فعل خطيرة بالجلد بما في ذلك متلازمة ستيفنز جونسون (SJS) و انحلال البشرة السامة (TEN) بالاشتراك مع علاج إيبويتين. يمكن أن تظهر متلازمة SJS / TEN في البداية في صورة بقع ذات احمرار أو بقع دائرية في كثير من الأحيان مع بثور مركزية على الجذع. يمكن أن يحدث أيضا قرحات بالفم، بالحلق، بالأنف، بالأعضاء التناسلية وبالعينين (احمرار وتورم العينين). وغالبا ما يسبق الطفح الجلدي الخطير أعراض حمى و / أو أعراض تشبه الإنفلونزا. قد يتطور الطفح الجلدي إلى تقشير الجلد على نطاق واسع ومضاعفات تهدد الحياة.

إذا كنت تعاني من طفح جلدي أو أي من هذه الأعراض، توقف عن تناول أرانسب واتصل بطبيبك أو اطلب العناية الطبية فورا.

 

أدوية أخرى وأرانسب

 

يرجى أن تخبر طبيبك أو الصيدلي إن كنت تتناول أو تناولت مؤخرا أو بإمكانك تناول أي أدوية أخرى.

 

يمكن أن يتأثر دواء سايكلوسبورين ودواء تاكروليماس (وهي أدوية تقمع جهاز المناعة) بعدد خلايا الدم الحمراء في جسمك. ويجب أن تخبر طبيبك إذا كنت تتناول أيا من هذه الأدوية.

 

استخدام أرانسب مع الطعام والشراب

 

الطعام والشراب لا يؤثران على أرانسب.

 

الحمل والرضاعة الطبيعية

 

إذا كنت حاملا أو ترضعين، تعتقدين أنك حاملا أو تخططين للحمل، من الضروري إخبار طبيبك أو الصيدلي قبل استخدام هذا الدواء.

 

لم يختبر أرانسب على النساء الحوامل. ويجب أن تخبري طبيبك في الحالات التالية:

·             إذا كنت حاملا،

·             إذا كنت تعتقدين أنك ربما تكونين حاملا، أو

·             إذا كنت تنوين الحمل.

 

ليس معروفا ما إذا كانت مادة داربيبويتين ألفا يتم إفرازها في لبن الأم. لذا يجب أن تتوقفي عن الإرضاع إذا كنت تستخدمين دواء أرانسب.

 

قيادة السيارات واستخدام الآلات

 

لا يؤثر أرانسب على قدرتك على قيادة السيارة أو استخدام الآلات.

 

يحتوي أرانسب على الصوديوم

 

هذا المنتج الطبي يحتوي على أقل من ١ مليمول من الصوديوم (٢٣ مجم) في الجرعة الواحدة، أي أنه في الأساس "خال من الصوديوم".

https://localhost:44358/Dashboard

استخدم دائما هذا الدواء تماما كما حدثك طبيبك أو الصيدلي. استشر طبيبك أو الصيدلي إذا كنت غير متأكدا.

 

حقن نفسك بأرانسب

 

لطبيبك الحق في تقرير ما إذا كنت تستطيع أن تتناول الجرعة بنفسك أو أن يناولها لك الممرض(ة). وسيعلمك الطبيب، أو الممرض(ة)، أو الصيدلي كيف تحقن نفسك باستخدام الحقنة المملوءة مسبقا. ولا تحاول أن تحقن نفسك إذا كنت غير مدرب على ذلك. لا تحقن أبدا أرانسب في الوريد بنفسك.

 

إذا كنت تعاني من فشل كلوي مزمن

 

بعد إجراء فحوصات الدم، يقرر طبيبك المعالج مدى احتياجك لأرانسب عندما يكون مستوى الهيموجلوبين في الدم ١٠ جم/ديسيلتر أو أقل. وسيرشدك الطبيب إلى الجرعة التي يجب أن تتناولها من أرانسب وعدد الجرعات المطلوبة للحفاظ على مستوى الهيموجلوبين في دمك ما بين ١٠ و١١ جم/ديسيلتر. وتختلف الجرعات ومعدلات تناولها بناء على المرحلة العمرية إذا كنت من البالغين أو الأطفال.

 

بالنسبة لجميع المرضى البالغين والأطفال البالغين من العمر سنة واحدة فما فوق، والذين يعانون من الفشل الكلوي المزمن، يستخدم أرانسب في شكل حقنة واحدة، إما تحت الجلد أو في الوريد.

 

لعلاجك من فقر الدم، يتم تحديد الجرعة الأولية من أرانسب لكل كيلوجرام من وزن الجسم، وذلك بإحدى الطريقتين التاليتين:

·             تحقن جرعة ٠٫٧٥ ميكروجرام مرة كل أسبوعين، أو

·             تحقن جرعة ٠٫٤٥ ميكروجرام مرة واحدة كل أسبوع.

 

بالنسبة للمرضى البالغين الذين لا يخضعون لغسيل الكلى، فإنه يمكن استخدام ١٫٥ ميكروجرام/كغ مرة واحدة في الشهر كجرعة أولية.

 

بالنسبة لجميع المرضى البالغين والأطفال البالغين من العمر سنة واحدة فما فوق، والذين يعانون من الفشل الكلوي المزمن، حالما يتم تصحيح فقر الدم، سوف تستمر في تلقي أرانسب في شكل حقنة واحدة، إما مرة واحدة في الأسبوع أو مرة كل أسبوعين. بالنسبة لجميع المرضى البالغين والأطفال البالغين من العمر ۱۱ عاما فما فوق، الذين لا يخضعون لغسيل الكلى، يمكنهم أيضا استخدام أرانسب مرة واحدة في الشهر.

 

سيأخذ طبيبك عينة من دمك بانتظام لقياس مدى استجابة فقر الدم لديك للعلاج، ويمكن أن يعدل الجرعة مرة واحدة كل أربعة أسابيع إن لزم الأمر من أجل الحفاظ على التحكم في فقر الدم الخاص بك على المدى الطويل.

 

وعندما يتم تصحيح حالة فقر الدم، سيستمر طبيبك في إجراء فحوصات الدم المطلوبة لك على نحو منتظم، ويمكن أن يتم تعديل الجرعة بعد ذلك من أجل التحكم في مستوى فقر الدم لديك على المدى الطويل. وسيبلغك طبيبك في حالة تغيير الجرعة.

 

سوف يستخدم طبيبك أقل جرعة فعالة ممكنة للتحكم في أعراض فقر الدم لديك.

 

إذا كنت لا تستجيب كما ينبغي لأرانسب، سوف يتحقق طبيبك من الجرعة الخاصة بك وسوف يبلغك إذا كنت بحاجة إلى تغيير جرعات أرانسب.

 

كما سيتم فحص ضغط الدم لديك على نحو منتظم، وخاصة في بداية علاجك.

 

في بعض الحالات، يمكن لطبيبك أن يوصي بتناولك لأحد الأدوية التي تحتوي على الحديد.

 

ويمكن لطبيبك أن يقرر تغيير طريقة حقنك (إما تحت الجلد أو في الوريد). وفي حالة التغيير، ستبدأ بتناول نفس الجرعة التي كنت تتناولها، وسيأخذ طبيبك عينات من دمك فيما بعد للتأكد من التحكم في مستوى فقر الدم لديك على نحو صحيح.

 

إذا قرر طبيبك تغيير نظامك العلاجي من r-HuEPO (الإريثروبويتين التي تنتجها تكنولوجيا الجينات) إلى أرانسب فسيختار بين إعطائك جرعة أسبوعية من دواء أرانسب أو جرعة كل أسبوعين من هذا الدواء. طريقة حقن أرانسب هي نفس الطريقة المستخدمة لحقن r-HuEPO، ولكن سيخبرك طبيبك بالجرعة الواجب تناولها، وتوقيتها، كما يمكن أن يعدل الجرعة إن لزم الأمر.

 

إذا كنت تتلقى علاجا كيميائيا

 

بعد إجراء فحوصات الدم، يقرر طبيبك المعالج مدى احتياجك لارانسب عندما يكون مستوى الهيموجلوبين في الدم ١٠ جم/ديسيلتر أو أقل. وسيرشدك الطبيب إلى الجرعة التي يجب أن تتناولها من أرانسب وعدد الجرعات المطلوبة للحفاظ على مستوى الهيموجلوبين ما بين ١٠ و١٢ جم/ديسيلتر.

 

يتم حقن دواء أرانسب تحت الجلد كجرعة واحدة، إما مرة واحدة كل أسبوع أو كل ثلاثة أسابيع.

 

ومن أجل شفائك التام من فقر الدم، ستكون الجرعة الأولية على أي من النظامين التاليين:

·             ٥٠٠ ميكروجرام مرة واحدة كل ثلاث أسابيع (٦٫٧٥ ميكروجرام من أرانسب عن كل كيلوجرام من وزن جسمك)، أو

·             أو ٢٫٢٥ ميكروجرام من أرانسب (مرة كل أسبوع) عن كل كيلوجرام من وزن جسمك.

 

سيأخذ طبيبك عينات من دمك على نحو منتظم لقياس مدى استجابة فقر الدم لديك للعلاج، ويمكن أن يعدل الجرعة إن لزم الأمر. وسيمتد علاجك لمدة أربعة أسابيع تقريبا بعد الانتهاء من تلقي العلاج الكيميائي. وسيخبرك طبيبك بالوقت المحدد لإيقاف العلاج بأرانسب.

 

في بعض الحالات، يمكن لطبيبك أن يوصي بتناولك لأحد الأدوية التي تحتوي على الحديد.

 

في حالة الإفراط في استخدام أرانسب

 

يمكن أن تواجه مشاكل خطيرة في حالة استخدام جرعة زائدة عن المطلوب من أرانسب، مثل ارتفاع ضغط الدم. يجب عليك الاتصال بالطبيب أو الممرض(ة) أو الصيدلي في حالة حدوث مثل هذا الأمر. ويجب عليك الاتصال على الفور بالطبيب أو الممرض(ة) أو الصيدلي عند شعورك بالتوعك بأي شكلِ من الأشكال.

 

في حالة نسيان استخدام أرانسب

 

لا تستخدم جرعة مضاعفة لتعويض الجرعة المنسية.

 

يجب عليك الاتصال بطبيبك في حالة نسيان استخدام جرعة من أرانسب، وذلك لمناقشة الأمر معه لمعرفة موعد حقن الجرعة القادمة.

 

في حالة التوقف عن استخدام أرانسب

 

إذا كنت ترغب في التوقف عن استخدام أرانسب، يجب عليك مناقشة هذا الأمر مع طبيبك أولا.

 

مثل كافة الأدوية، يمكن لهذا الدواء أن يسبب آثارا جانبية، رغم أنها لا تظهر لدى كافة المرضى.

 

ظهرت الآثار الجانبية التالية على بعض المرضى الذين استخدموا أرانسب:

 

مرضى الفشل الكلوي المزمن

 

آثار جانبية شائعة جدا: قد تؤثر على أكثر من ١ عن كل ١٠ أشخاص

·             ارتفاع ضغط الدم (فرط الضغط)

·             حساسية

 

آثار جانبية شائعة: قد تؤثر على ١ عن كل ١٠ أشخاص

·             سكتة دماغية

·             ألم حول المنطقة التي يتم حقنها

·             حكة أو احمرار في الجلد أو كليهما

 

آثار جانبية غير شائعة: قد تؤثر على ١ عن كل ١٠٠ شخص

·             جلطات الدم (التجلطات)

·             اختلاجات (النوبات والتشنجات)

·             كدمات و نزيف في موقع الحقن

·             جلطات الدم في فتحة دخول أنبوب غسيل الكلى

 

من غير المعروف: لا يمكن تقدير التكرار بناء على المعلومات المتاحة

·             عدم تنسج الكريات الحمراء النقي (PRCA) - (فقر الدم، إرهاق غير معتاد، فقدان النشاط)

 

مرضى السرطان

 

آثار جانبية شائعة جدا: قد تؤثر على أكثر من ١ عن كل ١٠ أشخاص

·             حساسية

 

آثار جانبية شائعة: قد تؤثر على ١ عن كل ١٠ أشخاص

·             ارتفاع ضغط الدم (فرط الضغط)

·             جلطات الدم (التجلطات)

·             ألم حول المنطقة التي يتم حقنها

·             حكة أو احمرار في الجلد أو كليهما

·             احتباس السوائل (وَذمة)

 

آثار جانبية غير شائعة: قد تؤثر على ١ عن كل ١٠٠ شخص

·             اختلاجات (النوبات والتشنجات)

·             كدمات و نزيف في موقع الحقن

 

جميع المرضى

 

من غير المعروف: لا يمكن تقدير التكرار بناء على المعلومات المتاحة

·             تفاعلات حساسية خطيرة قد تشمل:

·              تفاعلات حساسية مفاجئة تهدد البقاء على قيد الحياة (فرط الحساسية)

·              حالات تورم في الوجه أو الشفاه أو الفم أو اللسان أو الحلق، مما قد يؤدي إلى صعوبة في البلع أو التنفس (وذمة وعائية)

·              ضيق التنفس (تشنج قصبي تحسسي)

·              حكة في الجلد

·              شَرَى (الارتكاريا)

·             تم الإبلاغ عن ردود فعل خطيرة بالجلد بما في ذلك متلازمة ستيفنز جونسون (SJS) و انحلال البشرة السامة (TEN) بالاشتراك مع علاج إيبويتين. يمكن أن تظهرهذه ردود الفعل في صورة بقع ذات احمرار أو بقع دائرية في كثير من الأحيان مع ظهور بثور مركزية على الجذع، تقشير الجلد، وقرحات بالفم والحلق والأنف والأعضاء التناسلية والعينين ويمكن أن يسبقه حمى وأعراض شبيهة بأعراض الانفلونزا.

يجب التوقف عن استخدام أرانسب إذا كنت تعاني من هذه الأعراض والاتصال بطبيبك أو التماس العناية الطبية على الفور. انظر أيضا القسم ٢.

 

الإبلاغ عن الآثار الجانبیة

 

إذا تعرضت لأي آثار جانبیة، یرجى إبلاغ طبیبك أو الصیدلي أو الممرض(ة). ویشمل ذلك أي آثار جانبیة غیر مدرجة في ھذه النشرة. من خلال الإبلاغ عن الآثار الجانبیة، یمكنك أن تساعد في توفیر مزید من المعلومات حول سلامة ھذا الدواء.

 

يُحفظ هذا الدواء بعيدا عن مرأى ومتناول الأطفال.

 

لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المدون على العبوة وعلى البطاقة المثبتة على الحقنة المملوءة مسبقا بعد كلمة "EXP". ويشير تاريخ انتهاء الصلاحية إلى آخر يوم من ذلك الشهر.

 

يُحفظ الدواء في الثلاجة (٢ م ‑ ٨ م)، ولا يجب تجميده. ويمنع استخدامه إذا ظننت أنه تعرض للتجميد.

 

وتخزن الحقنة المملوءة مسبقا في عبوتها الخارجية الأصلية لحمايتها من الضوء.

 

ولأغراض الاستخدام المتنقل، يمكن إخراج أرانسب من مكان التخزين مرة واحدة لمدة أقصاها سبعة أيام في درجة حرارة الغرفة (حتى ۲٥°م). ما أن تخراج الحقنة من الثلاجة و ما أن تبلغ درجة حرارة الغرفة (تصل إلى ۲٥°م) يجب أن تستخدم إما في غضون ٧ أيام أو يجب التخلص منها.

 

لا تستخدم هذا الدواء إذا لاحظت أن محتويات الحقنة المملوءة مسبقا غائمة أو هناك عوالق بداخلها.

 

لا ينبغي التخلص من الأدوية عن طريق مياه الصرف أو نفايات المنزل، اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد تستعملها فهذه الإجراءات من شأنها الحفاظ على البيئة.

 

عما يحتوي أرانسب

 

-              إن المادة الفعالة هي داربيبويتن ألفا، r-HuEPO (الإريثروبويتين التي تنتجها تكنولوجيا الجينات). تحتوي الحقنة المملوءة مسبقا على ١٠ أو ٢٠ أو ٣٠ أو ٤٠ أو ٥٠ أو ٦٠ أو ٨٠ أو ١٠٠ أو ١٥٠ أو ٣٠٠ أو ٥٠٠ ميكروجرام من داربيبويتن ألفا.

-              المكونات الأخرى: يحتوي كل ١ مل على بولي سوربات ٨٠ (٠٫٠٥ مجم)، فوسفات الصوديوم أحادي القاعدة مونوهيدرات (٢٫١٢ مجم)، فوسفات الصوديوم اللامائية ثنائي القاعدة (٠٫٦٦ مجم)، كلوريد الصوديوم (٨٫١٨ مجم) في ماء للحقن (حتى ١ مل).

الشكل الخارجي لأرانسب ومحتويات العبوة

 

أرانسب هو عبارة عن سائل صافي عديم اللون أو لونه لؤلؤي بدرجة بسيطة للحقن في حقنة مملوءة مسبقا.

 

يتوفر ارانسب في عبوات تحتوي على حقنة واحدة أو أربع حقنات معبأة مسبقا مغلفة. تقدم الحقن إما مغلفة (عبوة ١ أو ٤ حقن) أو غير مغلفة (عبوة حقنة واحدة). قد لا تطرح كافة أحجام العبوات في الأسواق.

 

صاحب ترخيص التسويق والمصنع:

‪Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

هولندا

 

لمزيد من المعلومات عن هذا الدواء، يرجى الاتصال بالممثل المحلي للشركة والمفوض بتسويق الدواء.

 

تم مراجعة هذه النشرة بتاريخ نوفمبر ٢٠۱٩.
 Read this leaflet carefully before you start using this product as it contains important information for you

Aranesp 10 micrograms solution for injection in pre-filled syringe. Aranesp 20 micrograms solution for injection in pre-filled syringe. Aranesp 30 micrograms solution for injection in pre-filled syringe. Aranesp 40 micrograms solution for injection in pre-filled syringe. Aranesp 50 micrograms solution for injection in pre-filled syringe. Aranesp 60 micrograms solution for injection in pre-filled syringe. Aranesp 80 micrograms solution for injection in pre-filled syringe. Aranesp 100 micrograms solution for injection in pre-filled syringe. Aranesp 150 micrograms solution for injection in pre-filled syringe. Aranesp 300 micrograms solution for injection in pre-filled syringe. Aranesp 500 micrograms solution for injection in pre-filled syringe.

Each pre-filled syringe contains 10 micrograms of darbepoetin alfa in 0.4 mL (25 mcg/mL). Each pre-filled syringe contains 20 micrograms of darbepoetin alfa in 0.5 mL (40 mcg/mL). Each pre-filled syringe contains 30 micrograms of darbepoetin alfa in 0.3 mL (100 mcg/mL). Each pre-filled syringe contains 40 micrograms of darbepoetin alfa in 0.4 mL (100 mcg/mL). Each pre-filled syringe contains 50 micrograms of darbepoetin alfa in 0.5 mL (100 mcg/mL). Each pre-filled syringe contains 60 micrograms of darbepoetin alfa in 0.3 mL (200 mcg/mL). Each pre-filled syringe contains 80 micrograms of darbepoetin alfa in 0.4 mL (200 mcg/mL). Each pre-filled syringe contains 100 micrograms of darbepoetin alfa in 0.5 mL (200 mcg/mL). Each pre-filled syringe contains 150 micrograms of darbepoetin alfa in 0.3 mL (500 mcg/mL). Each pre-filled syringe contains 300 micrograms of darbepoetin alfa in 0.6 mL (500 mcg/mL). Each pre-filled syringe contains 500 micrograms of darbepoetin alfa in 1 mL (500 mcg/mL). Darbepoetin alfa is produced by gene technology in Chinese Hamster Ovary Cells (CHO K1). Excipient with known effect: Each pre-filled syringe contains 1.52 mg of sodium in 0.4 mL. Each pre-filled syringe contains 1.90 mg of sodium in 0.5 mL. Each pre-filled syringe contains 1.14 mg of sodium in 0.3 mL. Each pre-filled syringe contains 1.52 mg of sodium in 0.4 mL. Each pre-filled syringe contains 1.90 mg of sodium in 0.5 mL. Each pre-filled syringe contains 1.14 mg of sodium in 0.3 mL. Each pre-filled syringe contains 1.52 mg of sodium in 0.4 mL. Each pre-filled syringe contains 1.90 mg of sodium in 0.5 mL. Each pre-filled syringe contains 1.14 mg of sodium in 0.3 mL. Each pre-filled syringe contains 2.27 mg of sodium in 0.6 mL. Each pre-filled syringe contains 3.79 mg of sodium in 1 mL. For the full list of excipients, see section 6.1.

Solution for injection (injection) in pre-filled syringe. Clear, colourless solution.

Treatment of symptomatic anaemia associated with chronic renal failure (CRF) in adults and paediatric patients (see section 4.2).

 

Treatment of symptomatic anaemia in adult cancer patients with non‑myeloid malignancies receiving chemotherapy.


Aranesp treatment should be initiated by physicians experienced in the above mentioned indications.

 

Posology

 

Treatment of symptomatic anaemia in adult and paediatric chronic renal failure patients

 

Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary. Aranesp should be administered either subcutaneously or intravenously in order to increase haemoglobin to not greater than 11 g/dL (6.8 mmol/L). Subcutaneous use is preferable in patients who are not receiving haemodialysis to avoid the puncture of peripheral veins.

 

Patients should be monitored closely to ensure that the lowest approved effective dose of Aranesp is used to provide adequate control of the symptoms of anaemia whilst maintaining a haemoglobin concentration below or at 11 g/dL (6.8 mmol/L). Caution should be exercised with escalation of Aranesp doses in patients with chronic renal failure. In patients with a poor haemoglobin response to Aranesp, alternative explanations for the poor response should be considered (see sections 4.4 and 5.1).

 

Due to intra‑patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dL (6.2 mmol/L) to 11 g/dL (6.8 mmol/L). A sustained haemoglobin level of greater than 11 g/dL (6.8 mmol/L) should be avoided; guidance for appropriate dose adjustment for when haemoglobin values exceeding 11 g/dL (6.8 mmol/L) are observed are described below. A rise in haemoglobin of greater than 2 g/dL (1.25 mmol/L) over a four week period should be avoided. If it occurs, appropriate dose adjustment should be made as provided.

 

Treatment with Aranesp is divided into two stages, correction and maintenance phase. Guidance is given separately for adult and paediatric patients.

 

Adult patients with chronic renal failure

 

Correction phase:

 

The initial dose by subcutaneous or intravenous administration is 0.45 mcg/kg body weight, as a single injection once weekly. Alternatively, in patients not on dialysis, the following initial doses can also be administered subcutaneously as a single injection: 0.75 mcg/kg once every two weeks or 1.5 mcg/kg once monthly. If the increase in haemoglobin is inadequate (less than 1 g/dL (0.6 mmol/L) in four weeks) increase the dose by approximately 25%. Dose increases must not be made more frequently than once every four weeks.

 

If the rise in haemoglobin is greater than 2 g/dL (1.25 mmol/L) in four weeks reduce the dose by approximately 25%. If the haemoglobin exceeds 11 g/dL (6.8 mmol/L), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.

 

The haemoglobin should be measured every one or two weeks until it is stable. Thereafter the haemoglobin can be measured at longer intervals.

 

Maintenance phase:

 

In dialysis patients, Aranesp may continue to be administered as a single injection once weekly or once every two weeks. Dialysis patients converting from once weekly to once every other week dosing with Aranesp should initially receive a dose equivalent to twice the previous once weekly dose.

 

In patients not on dialysis, Aranesp may continue to be administered as a single injection once weekly or once every two weeks or once monthly. For patients treated with Aranesp once every two weeks, after the target haemoglobin has been achieved, Aranesp may then be administered subcutaneously once monthly using an initial dose equal to twice the previous once every two week dose. 

 

Dosing should be titrated as necessary to maintain the haemoglobin target.

 

If a dose adjustment is required to maintain haemoglobin at the desired level, it is recommended that the dose is adjusted by approximately 25%.

 

If the rise in haemoglobin is greater than 2 g/dL (1.25 mmol/L) in four weeks reduce the dose by approximately 25%, depending on the rate of increase. If the haemoglobin exceeds 11 g/dL (6.8 mmol/L), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.

 

After any dose or schedule adjustment the haemoglobin should be monitored every one or two weeks. Dose changes in the maintenance phase of treatment should not be made more frequently than every two weeks.

 

When changing the route of administration the same dose must be used and the haemoglobin monitored every one or two weeks so that the appropriate dose adjustments can be made to keep the haemoglobin at the desired level.

 

Clinical studies have demonstrated that adult patients receiving r‑HuEPO one, two or three times weekly may be converted to once weekly or once every other week Aranesp. The initial weekly dose of Aranesp (mcg/week) can be determined by dividing the total weekly dose of r‑HuEPO (IU/week) by 200. The initial every other week dose of Aranesp (mcg/every other week) can be determined by dividing the total cumulative dose of r‑HuEPO administered over a two-week period by 200. Because of individual variability, titration to optimal therapeutic doses is expected for individual patients. When substituting Aranesp for r‑HuEPO the haemoglobin should be monitored every one or two weeks and the same route of administration should be used.

 

Paediatric population with chronic renal failure

 

Treatment of paediatric patients younger than 1 year of age has not been studied in randomised clinical trials (see section 5.1).

 

Correction phase:

 

For patients ≥ 1 year of age, the initial dose by subcutaneous or intravenous administration is 0.45 mcg/kg body weight, as a single injection once weekly. Alternatively, in patients not on dialysis, an initial dose of 0.75 mcg/kg may be administered subcutaneously as a single injection once every two weeks. If the increase in haemoglobin is inadequate (less than 1 g/dL (0.6 mmol/L) in four weeks) increase the dose by approximately 25%. Dose increases must not be made more frequently than once every four weeks.

 

If the rise in haemoglobin is greater than 2 g/dL (1.25 mmol/L) in four weeks reduce the dose by approximately 25%, depending on the rate of increase. If the haemoglobin exceeds 11 g/dL (6.8 mmol/L), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.

 

The haemoglobin should be measured every one or two weeks until it is stable. Thereafter the haemoglobin can be measured at longer intervals.

 

Correction of anaemia in paediatric patients with once monthly Aranesp dosing frequency has not been studied.

 

Maintenance phase:

 

For paediatric patients ≥ 1 year of age, in the maintenance phase, Aranesp may continue to be administered as a single injection once weekly or once every two weeks. Patients < 6 years of age may need higher doses for maintenance of haemoglobin than patients above that age. Dialysis patients converting from once weekly to once every other week dosing with Aranesp should initially receive a dose equivalent to twice the previous once weekly dose.

 

In patients ≥ 11 years of age not on dialysis, once the target haemoglobin has been achieved with once every two week dosing, Aranesp may be administered subcutaneously once monthly using an initial dose equal to twice the previous once every two week dose.

 

Clinical data in paediatric patients has demonstrated that patients receiving r‑HuEPO two or three times weekly may be converted to once weekly Aranesp, and those receiving r‑HuEPO once weekly may be converted to once every other week Aranesp. The initial weekly paediatric dose of Aranesp (mcg/week) can be determined by dividing the total weekly dose of r‑HuEPO (IU/week) by 240. The initial every other week dose of Aranesp (mcg/every other week) can be determined by dividing the total cumulative dose of r‑HuEPO administered over a two-week period by 240. Because of individual variability, titration to optimal therapeutic doses is expected for individual patients. When substituting Aranesp for r‑HuEPO the haemoglobin should be monitored every one or two weeks and the same route of administration should be used.

 

Dosing should be titrated as necessary to maintain the haemoglobin target.

 

If a dose adjustment is required to maintain haemoglobin at the desired level, it is recommended that the dose is adjusted by approximately 25%.

 

If the rise in haemoglobin is greater than 2 g/dL (1.25 mmol/L) in four weeks reduce the dose by approximately 25%, depending on the rate of increase. If the haemoglobin exceeds 11 g/dL (6.8 mmol/L), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.

 

Patients starting dialysis during treatment with Aranesp should be closely monitored for adequate control of their haemoglobin.

 

After any dose or schedule adjustment the haemoglobin should be monitored every one or two weeks. Dose changes in the maintenance phase of treatment should not be made more frequently than every two weeks.

 

When changing the route of administration the same dose must be used and the haemoglobin monitored every one or two weeks so that the appropriate dose adjustments can be made to keep the haemoglobin at the desired level.

 

Treatment of symptomatic chemotherapy‑induced anaemia in cancer patients

 

Aranesp should be administered by the subcutaneous route to patients with anaemia (e.g.haemoglobin concentration ≤ 10 g/dL (6.2 mmol/L)) in order to increase haemoglobin to not greater than 12 g/dL (7.5 mmol/L). Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary. 

 

Due to intra‑patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dL (6.2 mmol/L) to 12 g/dL (7.5 mmol/L). A sustained haemoglobin level of greater than 12 g/dL (7.5 mmol/L) should be avoided; guidance for appropriate dose adjustments for when haemoglobin values exceeding 12 g/dL (7.5 mmol/L) are observed are described below.

 

The recommended initial dose is 500 mcg (6.75 mcg/kg) given once every three weeks, or once weekly dosing can be given at 2.25 mcg/kg body weight. If the clinical response of the patient (fatigue, haemoglobin response) is inadequate after nine weeks, further therapy may not be effective.

 

Aranesp therapy should be discontinued approximately four weeks after the end of chemotherapy.

 

Once the therapeutic objective for an individual patient has been achieved, the dose should be reduced by 25 to 50% in order to ensure that the lowest approved dose of Aranesp is used to maintain haemoglobin at a level that controls the symptoms of anaemia. Appropriate dose titration between 500 mcg, 300 mcg, and 150 mcg should be considered.

 

Patients should be monitored closely, if the haemoglobin exceeds 12 g/dL (7.5 mmol/L), the dose should be reduced by approximately 25 to 50%. Treatment with Aranesp should be temporarily discontinued if haemoglobin levels exceed 13 g/dL (8.1 mmol/L). Therapy should be reinitiated at approximately 25% lower than the previous dose after haemoglobin levels fall to 12 g/dL (7.5 mmol/L) or below.

 

If the rise in haemoglobin is greater than 2 g/dL (1.25 mmol/L) in 4 weeks, the dose should be reduced by 25 to 50%.

 

Method of administration

 

Aranesp may be administered subcutaneously by the patient or a carer after being trained by a doctor, nurse or pharmacist.

 

Aranesp 10, 20, 30, 40, 50, 60, 80, 100, 150, 300, 500 micrograms solution for injection in pre-filled syringe

Aranesp is administered either subcutaneously or intravenously as described in the posology.

Rotate the injection sites and inject slowly to avoid discomfort at the site of injection.

Aranesp is supplied ready for use in a pre‑filled syringe.

 

The instructions for use, handling and disposal are given in section 6.6.

 


Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Poorly controlled hypertension.

 

 

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOUR PROGRESSION OR RECURRENCE

 

Chronic Renal Failure:

·        In controlled trials, patients experienced greater risks for death, serious

cardiovascular reactions, and stroke when administered erythropoiesis-stimulating

agents (ESAs) to target a haemoglobin level of greater than 11 g/dL.

·        No trial has identified a haemoglobin target level, Aranesp dose, or dosing strategy that does not increase these risks.

·        Use the lowest Aranesp dose sufficient to reduce the need for red blood cell (RBC) transfusions.

 

Cancer:

·        ESAs shortened overall survival and/or increased the risk of tumour progression

or recurrence in clinical studies of patients with breast, non‑small celllung, head and neck, lymphoid, and cervical cancers.

·        Use the lowest dose to avoid red blood cell transfusions.

·        Use ESAs only for anaemia from myelosuppressive chemotherapy.

·        ESAs are not indicated for patients receiving myelosuppressive chemotherapy when

the anticipated outcome is cure.

·        Discontinue following the completion of a chemotherapy course.

 

 

General

 

In order to improve the traceability of erythropoiesis‑stimulating agents (ESAs), the trade name of the administered ESA should be clearly recorded (or stated) in the patient file.

 

Blood pressure should be monitored in all patients, particularly during initiation of Aranesp therapy. If blood pressure is difficult to control by initiation of appropriate measures, the haemoglobin may be reduced by decreasing or withholding the dose of Aranesp (see section 4.2). Cases of severe hypertension, including hypertensive crisis, hypertensive encephalopathy, and seizures, have been observed in CRF patients treated with Aranesp.

 

In order to ensure effective erythropoiesis, iron status should be evaluated for all patients prior to and during treatment and supplementary iron therapy may be necessary.

 

Non‑response to therapy with Aranesp should prompt a search for causative factors. Deficiencies of iron, folic acid or vitamin B12 reduce the effectiveness of ESAs and should therefore be corrected. Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminium toxicity, underlying haematologic diseases, or bone marrow fibrosis may also compromise the erythropoietic response. A reticulocyte count should be considered as part of the evaluation. If typical causes of non‑response are excluded, and the patient has reticulocytopenia, an examination of the bone marrow should be considered. If the bone marrow is consistent with PRCA, testing for anti‑erythropoietin antibodies should be performed.

 

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with epoetin treatment. More severe cases have been observed with long-acting epoetins.

At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Aranesp should be withdrawn immediately and an alternative treatment considered.

If the patient has developed a severe cutaneous skin reaction such as SJS or TEN due to the use of Aranesp, treatment with Aranesp must not be restarted in this patient at any time.

 

Pure red cell aplasia caused by neutralising anti‑erythropoietin antibodies has been reported in association with ESAs, including Aranesp. This has been predominantly reported in patients with CRF treated subcutaneously. These antibodies have been shown to cross‑react with all erythropoietic proteins, and patients suspected or confirmed to have neutralising antibodies to erythropoietin should not be switched to Aranesp (see section 4.8).

 

A paradoxical decrease in haemoglobin and development of severe anaemia associated with low reticulocyte counts should prompt to discontinue treatment with epoetin and perform anti‑erythropoietin antibody testing. Cases have been reported in patients with hepatitis C treated with interferon and ribavirin, when epoetins are used concomitantly. Epoetins are not approved in the management of anaemia associated with hepatitis C.

 

Active liver disease was an exclusion criteria in all studies of Aranesp, therefore no data are available from patients with impaired liver function. Since the liver is thought to be the principal route of elimination of darbepoetin alfa and r‑HuEPO, Aranesp should be used with caution in patients with liver disease.

 

Aranesp should also be used with caution in those patients with sickle cell anaemia.

 

Misuse of Aranesp by healthy persons may lead to an excessive increase in packed cell volume. This may be associated with life‑threatening complications of the cardiovascular system.

 

The needle cap of the pre‑filled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions.

 

In controlled clinical trials of patients with CRF comparing higher haemoglobin targets (13- 14 g/dL) to lower targets (9- 11.3 g/dL), Aranesp and other ESAs increased the risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of haemodialysis vascular access, and other thromboembolic events in the higher target groups.

 

In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopaedic procedures.

 

Aranesp should be used with caution in patients with epilepsy. Convulsions have been reported in patients receiving Aranesp.

 

The reported risk of thrombotic vascular events (TVEs) should be carefully weighed against the benefits to be derived from treatment with darbepoetin alfa particularly in patients with pre-existing risk factors for TVE, including obesity and prior history of TVEs (e.g., deep venous thrombosis, pulmonary embolism, and cerebral vascular accident).

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium‑free’.

 

Chronic renal failure patients

 

In controlled clinical trials of patients with CRF comparing higher haemoglobin targets (13-14 g/dL) to lower targets (9-11.3 g/dL), Aranesp and other ESAs increased the risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of haemodialysis vascular access, and other thromboembolic events in the higher target groups.

 

Using Aranesp to target a haemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in patients with coexistent cardiovascular disease and stroke. Patients with chronic renal failure and an insufficient haemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of haemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks.

 

Caution should be exercised with escalation of Aranesp doses in patients with chronic renal failure, since high cumulative epoetin doses may be associated with an increased risk of mortality, serious cardiovascular and cerebrovascular events. In patients with a poor haemoglobin response to epoetins, alternative explanations for the poor response should be considered (see sections 4.2 and 5.1).

 

Controlled clinical trials have not shown significant benefits attributable to the administration of epoetins when haemoglobin concentration is increased beyond the level necessary to control symptoms of anaemia and to avoid blood transfusion.

 

Supplementary iron therapy is recommended for all patients with serum ferritin values below 100 mcg/L or whose transferrin saturation is below 20%.

 

Serum potassium levels should be monitored regularly during Aranesp therapy. Potassium elevation has been reported in a few patients receiving Aranesp, though causality has not been established. If an elevated or rising potassium level is observed then consideration should be given to ceasing Aranesp administration until the level has been corrected.

 

Cancer patients

 

Effect on tumour growth

 

Epoetins are growth factors that primarily stimulate red blood cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumour cells. As with all growth factors, there is a concern that epoetins could stimulate the growth of tumours. In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anaemia associated with cancer.

 

In controlled clinical studies, use of Aranesp and other ESAs have shown:

 

·             shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin of greater than 14 g/dL (8.7 mmol/L), ESAs are not indicated for use in this patient population.

 

·             shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/dL (7.5-8.7 mmol/L).

 

·             increased risk of death and serious adverse cardiovascular reactions (including myocardial infarction and stroke) when administered to target a haemoglobin of 12 g/dL (7.5 mmol/L) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for use in this patient population.

 

·             an observed 9% increase in risk for PD or death in the epoetin alfa plus SOC group from a primary analysis and a 15% increased risk that cannot be statistically ruled out in patients with metastatic breast cancer receiving chemotherapy when administered to achieve a haemoglobin concentration range of 10 to 12 g/dL (6.2 to 7.5 mmol/L).

 

·             non-inferiority of darbepoetin alfa to placebo for overall survival and progression free survival in patients with advanced stage non-small cell lung cancer receiving chemotherapy when administered to a target haemoglobin of 12 g/dL (7.5 mmol/L) (see section 5.1).

 

In view of the above, in some clinical situations blood transfusion should be the preferred treatment for the management of anaemia in patients with cancer. The decision to administer recombinant erythropoietins should be based on a benefit-risk assessment with the participation of the individual patient, which should take into account the specific clinical context. Factors that should be considered in this assessment should include the type of tumour and its stage; the degree of anaemia; life‑expectancy; the environment in which the patient is being treated; and patient preference (see section 5.1).

 

In patients with solid tumours or lymphoproliferative malignancies, if the haemoglobin value exceeds 12 g/dL (7.5 mmol/L), the dosage adaptation described in section 4.2 should be closely respected, in order to minimise the potential risk of thromboembolic events. Platelet counts and haemoglobin level should also be monitored at regular intervals.

 


The clinical results obtained so far do not indicate any interaction of darbepoetin alfa with other substances. However, there is potential for an interaction with substances that are highly bound to red blood cells e.g. cyclosporin, tacrolimus. If Aranesp is given concomitantly with any of these treatments, blood levels of these substances should be monitored and the dosage adjusted as the haemoglobin rises.


Pregnancy

 

There are no adequate and well-controlled studies with Aranesp in pregnant women.

 

Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. No alteration of fertility was detected.

 

Caution should be exercised when prescribing Aranesp to pregnant women.

 

Breast-feeding

 

It is unknown whether Aranesp is excreted in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Aranesp therapy taking into account the benefit of breast‑feeding for the child and the benefit of therapy for the woman.


Aranesp has no or negligible influence on the ability to drive and use machines.


Summary of the safety profile

 

Identified adverse reactions associated with Aranesp are hypertension, stroke, thromboembolic events, convulsions, allergic reactions, rash/erythema and pure red cell aplasia (PRCA); see section 4.4.

 

Injection site pain was reported as attributable to treatment in studies where Aranesp was administered via subcutaneous injection. The injection site discomfort was generally mild and transient in nature and occurred predominantly after the first injection.

 

Tabulated list of adverse reactions

 

Incidence of adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: Very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

 

Data are presented separately for CRF and cancer patients reflecting the different adverse reaction profile in these populations.

 

Chronic renal failure patients

 

Data presented from controlled studies included 1,357 patients, 766 who received Aranesp and 591 patients who received r‑HuEPO. In the Aranesp group, 83% were receiving dialysis and 17% were not receiving dialysis. Stroke was identified as an adverse reaction in an additional clinical study (TREAT, see section 5.1).

 

Incidence of adverse reactions from controlled clinical studies and post-marketing experience are:

 

MedDRA system organ class

Subject incidence

Adverse reaction

Blood and lymphatic system disorders

Not known2

Pure red cell aplasia

Immune system disorders

Very common

Hypersensitivitya

Nervous system disorders

Common

Strokeb

 

Uncommon1

Convulsions

Cardiac disorders

Very common

Hypertension

Vascular disorders

Uncommon

Thromboembolic eventsc

Uncommon1

Dialysis vascular access thrombosisd

Skin and subcutaneous tissue disorders

Common

Rash/erythemae

Not known2

SJS/TEN, erythema multiforme, blistering, skin exfoliation

General disorders and administration site conditions

Common

Injection site pain

Uncommon1

Injection site bruising

Injection site haemorrhage

Source: Includes 5 randomised, double-blind, active-controlled studies (970200, 970235, 980117, 980202, and 980211) except for the adverse reaction of stroke which was identified as an adverse reaction in the TREAT study (study 20010184).

1 Adverse reactions identified in the post-marketing environment. Per the Guideline on Summary of Product Characteristics (Revision 2, September 2009), frequency of adverse reactions identified in the post-marketing setting was determined using the “Rule of three”.

2 Frequency cannot be estimated from the available data.

a Hypersensitivity events includes all events under the hypersensitivity SMQ.

b Stroke events includes PT haemorrhagic stroke, ischaemic stroke, cerebrovascular accident, and stroke in evolution.

c Thromboembolic events adverse reaction includes PT embolism arterial, thrombophlebitis, thrombosis, venous thrombosis limb.

d Dialysis vascular access thrombosis includes all adverse reactions under the dialysis vascular access thrombosis AMQ.

e Rash/erythema adverse reaction includes PT rash, rash pruritic, rash macular, rash generalised, erythema.

 

Cancer patients

 

Adverse reactions were determined based on pooled data from eight randomised, double‑blind, placebo‑controlled studies of Aranesp with a total of 4,630  patients (Aranesp 2,888, placebo 1,742). Patients with solid tumours (e.g., lung, breast, colon, ovarian cancers) and lymphoid malignancies (e.g., lymphoma, multiple myeloma) were enrolled in the clinical studies.

 

Incidence of adverse reactions from controlled clinical studies and post-marketing experience are:

 

MedDRA system organ class

Subject incidence

Adverse reaction

Immune system disorders

Very common

Hypersensitivitya

Nervous system disorders

Uncommon1

Convulsions

Cardiac disorders

Common

Hypertension

Vascular disorders

Common

Thromboembolic eventsb, including pulmonary embolism

Skin and subcutaneous tissue disorders

Common

Rash/erythemac

Not known2

SJS/TEN, erythema multiforme, blistering, skin exfoliation

General disorders and administration site conditions

Common

Oedemad

Common

Injection site paine

Uncommon1

Injection site bruising

Injection site haemorrhage

1 ADRs identified in the post-marketing environment. Per the Guideline on Summary of Product Characteristics (Revision 2, September 2009), frequency of ADRs identified in the post-marketing setting was determined using the “Rule of three”.

2 Frequency cannot be estimated from the available data.

Source: includes 8 randomised, double-blind, placebo-controlled studies (980291-schedule 1 and 2, 980297, 990114, 20000161, 20010145, 20030232, and 20070782).

a Hypersensitivity events includes all events under the hypersensitivity SMQ.

b Thromboembolic events adverse reactions includes PT embolism, thrombosis, deep vein thrombosis, jugular vein thrombosis, venous thrombosis, arterial thrombosis, pelvic venous thrombosis, peripheral embolism, pulmonary embolism, as well as thrombosis in device from SOC product issues.

c Rash adverse reactions includes PT rash, rash pruritic, rash generalised, rash papular, erythema, exfoliative rash, rash maculo-papular, rash vesicular as well as rash pustular from SOC Infections and Infestations.

d Oedema: includes PT Oedema Peripheral, Oedema, Generalised Oedema, Oedema due to Cardiac Disease, Face oedema.

e Injection site pain adverse reaction includes PT injection site pain, administration site pain, catheter site pain, infusion site pain and vessel puncture site pain.

 

Description of selected adverse reactions

 

Chronic renal failure patients

 

Stroke was reported as common in CRF patients in TREAT (see section 5.1).

 

In isolated cases, neutralising anti‑erythropoietin antibody mediated pure red cell aplasia (PRCA) associated with Aranesp therapy have been reported predominantly in patients with CRF treated subcutaneously. In case PRCA is diagnosed, therapy with Aranesp must be discontinued and patients should not be switched to another recombinant erythropoietic protein (see section 4.4).

 

The frequency of all hypersensitivity reactions was estimated from clinical trial data as very common in CRF patients. Hypersensitivity reactions were also very common in the placebo groups. There have been reports, from post-marketing experience, of serious hypersensitivity reactions including anaphylactic reaction, angioedema, allergic bronchospasm, skin rash and urticaria associated with darbepoetin alfa.

 

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported (see section 4.4).

 

Convulsions have been reported in patients receiving darbepoetin alfa (see section 4.4). The frequency is estimated from clinical trial data as uncommon in CRF patients.

 

In CRF patients on haemodialysis, events of vascular access thrombosis (such as vascular access complication, arteriovenous fistula thrombosis, graft thrombosis, shunt thrombosis, arteriovenous fistula site complication, etc.) have been reported in post-marketing data. The frequency is estimated from clinical trial data as uncommon.

 

Cancer patients

 

Hypertension has been observed in cancer patients in post-marketing experience (see section 4.4). The frequency is estimated from clinical trial data as common in cancer patients and was also common in the placebo groups.

 

Hypersensitivity reactions have been observed in cancer patients in post-marketing experience. The frequency of all hypersensitivity reactions was estimated from clinical trial data as very common in cancer patients. Hypersensitivity reactions were also very common in the placebo groups. There have been reports of serious hypersensitivity reactions including anaphylactic reaction, angioedema, allergic bronchospasm, skin rash and urticaria associated with darbepoetin alfa.

 

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported (see section 4.4).

 

Convulsions have been reported in patients receiving darbepoetin alfa in post-marketing experience (see section 4.4). The frequency is estimated from clinical trial data as uncommon in cancer patients. Convulsions were common in the placebo groups.

 

Paediatric chronic renal failure population

 

In all paediatric CRF studies, there were no additional adverse reactions identified for paediatric patients compared to those previously reported for adult patients (see section 5.1).

 

Reporting of suspected adverse reactions

 

Reporting of 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 to their local representative.

 

Reporting to National Regulatory Authority:

To report any side effects:

Saudi Arabia

o The National Pharmacovigilance and Drug Safety Centre (NPC)

o Fax: +966-11-205-7662

o Call NPC at +966-11-2038222, Exts: 2317-2356-2340.

o SFDA Call Center: 19999

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

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

 


The maximum amount of Aranesp that can be safely administered in single or multiple doses has not been determined. Therapy with Aranesp can result in polycythaemia if the haemoglobin is not carefully monitored and the dose appropriately adjusted. Cases of severe hypertension have been observed following overdose with Aranesp (see section 4.4).

 

In the event of polycythaemia, Aranesp should be temporarily withheld (see section 4.2). If clinically indicated, phlebotomy may be performed.

 


Pharmacotherapeutic group: Anti‑anaemic preparations, other anti‑anaemic preparations, ATC Code: B03XA02.

 

Mechanism of action

 

Human erythropoietin is an endogenous glycoprotein hormone that is the primary regulator of erythropoiesis through specific interaction with the erythropoietin receptor on the erythroid progenitor cells in the bone marrow. The production of erythropoietin primarily occurs in and is regulated by the kidney in response to changes in tissue oxygenation. Production of endogenous erythropoietin is impaired in patients with chronic renal failure and the primary cause of their anaemia is due to erythropoietin deficiency. In patients with cancer receiving chemotherapy the etiology of anaemia is multifactorial. In these patients, erythropoietin deficiency and a reduced response of erythroid progenitor cells to endogenous erythropoietin both contribute significantly towards their anaemia.

 

Pharmacodynamic effects

 

Darbepoetin alfa stimulates erythropoiesis by the same mechanism as the endogenous hormone. Darbepoetin alfa has five N‑linked carbohydrate chains whereas the endogenous hormone and recombinant human erythropoietins (r‑HuEPO) have three. The additional sugar residues are molecularly indistinct from those on the endogenous hormone. Due to its increased carbohydrate content darbepoetin alfa has a longer terminal half‑life than r‑HuEPO and consequently a greater in vivo activity. Despite these molecular changes, darbepoetin alfa retains a very narrow specificity for the erythropoietin receptor.

 

Clinical efficacy and safety

 

Chronic renal failure patients

 

Patients with CRF experienced greater risks for death and serious cardiovascular events when administered ESAs to target higher versus lower haemoglobin levels (13.5 g/dL (8.4 mmol/L) versus 11.3 g/dL (7.1 mmol/L); 14 g/dL (8.7 mmol/L) versus 10 g/dL (6.2 mmol/L) in two clinical studies.

 

In a randomised, double-blind correction study (n = 358) comparing once every two week and once monthly dosing schedules in patients with CRF not on dialysis, darbepoetin alfa once monthly dosing was non-inferior to once every two week dosing for correcting anaemia. The median (quartile 1, quartile 3) time to achieve haemoglobin correction (≥ 10.0 g/dL and ≥ 1.0 g/dL increase from baseline) was 5 weeks for both once every two week (3, 7 weeks) and once monthly dosing (3, 9 weeks). During the evaluation period (weeks 29‑33), the mean (95% CI) weekly equivalent dose was 0.20 (0.17, 0.24) mcg/kg in the once every two week arm and 0.27 (0.23, 0.32) mcg/kg in the once monthly arm.

 

In a randomised, double‑blind, placebo‑controlled study (TREAT) of 4,038 CRF patients not on dialysis with type 2 diabetes and haemoglobin levels ≤ 11 g/dL, patients received either treatment with darbepoetin alfa to target haemoglobin levels of 13 g/dL or placebo (with darbepoetin alfa rescue at haemoglobin less than 9 g/dL). The study did not meet either primary objective of demonstrating a reduction in risk for all‑cause mortality or cardiovascular morbidity (darbepoetin alfa vs placebo; HR 1.05, 95% CI (0.94, 1.17)), or all‑cause mortality or end stage renal disease (ESRD) (darbepoetin alfa vs placebo; HR 1.06, 95% CI (0.95, 1.19)). Analysis of the individual components of the composite endpoints showed the following HR (95% CI): death 1.05 (0.92, 1.21), congestive heart failure (CHF) 0.89 (0.74, 1.08), myocardial infarction (MI) 0.96 (0.75, 1.23), stroke 1.92 (1.38, 2.68), hospitalisation for myocardial ischaemia 0.84 (0.55, 1.27), ESRD 1.02 (0.87, 1.18).

 

Pooled post-hoc analyses of clinical studies of ESAs have been performed in chronic renal failure patients (on dialysis, not on dialysis, in diabetic and non-diabetic patients). A tendency towards increased risk estimates for all-cause mortality, cardiovascular and cerebrovascular events associated with higher cumulative ESA doses independent of the diabetes or dialysis status was observed (see sections 4.2 and 4.4). 

 

Paediatric population

 

In a randomised clinical study 114 paediatric patients aged 2 to 18 with chronic kidney disease receiving or not receiving dialysis who were anaemic (haemoglobin < 10.0 g/dL) and not being treated with an ESA were administered darbepoetin alfa weekly (n = 58) or once every two weeks (n = 56) for the correction of anaemia. Haemoglobin concentrations were corrected to ≥ 10 g/dL in > 98% (p < 0.001) of paediatric patients administered darbepoetin alfa once weekly and 84% (p = 0.293) once every two weeks. At the time haemoglobin ≥ 10.0 g/dL was first achieved, the mean (SD) weight‑adjusted dose was 0.48 (0.24) mcg/kg (range: 0.0 to 1.7 mcg/kg) weekly for the once weekly group and 0.76 (0.21) mcg/kg (range: 0.3 to 1.5 mcg/kg) biweekly for the once every two week group.

 

In a clinical study in 124 paediatric patients with chronic kidney disease receiving or not receiving dialysis aged 1 to 18, patients that were stable on epoetin alfa were randomised to receive either darbepoetin alfa administered once weekly (subcutaneously or intravenously) using a dose conversion ratio of 238:1 or to continue with epoetin alfa therapy at the current dose, schedule, and route of administration. The primary efficacy endpoint [change in haemoglobin between baseline and the evaluation period (week 21-28)] was comparable between the two groups. The mean haemoglobin for r‑HuEPO and darbepoetin alfa at baseline was 11.1 (SD 0.7) g/dL and 11.3 (SD 0.6) g/dL, respectively. The mean haemoglobin at week 28 for r‑HuEPO and darbepoetin alfa was 11.1 (SD 1.4) g/dL and 11.1 (SD 1.1) g/dL, respectively.

 

In an European observational registry study which enrolled 319 paediatric patients with chronic kidney disease (13 (4.1%) patients < 1 year of age, 83 (26.0%) patients 1‑< 6 years of age, 90 (28.2%) patients 6-< 12 years of age, and 133 (41.7%) patients ≥ 12 years of age) receiving darbepoetin alfa, mean haemoglobin concentrations ranging between 11.3 and 11.5 g/dL and mean weight-adjusted darbepoetin alfa doses remained relatively constant (between 2.31 mcg/kg month and 2.67 mcg/kg month) over the study period for the entire study population.

 

In these studies, no meaningful differences were identified between the safety profile for paediatric patients and that previously reported for adult patients (see section 4.8).

 

Cancer patients receiving chemotherapy

 

EPO-ANE-3010, a randomised, open-label, multicentre study was conducted in 2,098 anaemic women with metastatic breast cancer, who received first line or second line chemotherapy. This was a noninferiority study designed to rule out a 15% risk increase in tumour progression or death of epoetin alfa plus standard of care (SOC) as compared with SOC alone. At the time of clinical data cutoff, the median progression free survival (PFS) per investigator assessment of disease progression was 7.4 months in each arm (HR 1.09, 95% CI: 0.99, 1.20), indicating the study objective was not met. Significantly fewer patients received RBC transfusions in the epoetin alfa plus SOC arm (5.8% versus 11.4%); however, significantly more patients had thrombotic vascular events in the epoetin alfa plus SOC arm (2.8% versus 1.4%). At the final analysis, 1,653 deaths were reported. Median overall survival in the epoetin alfa plus SOC group was 17.8 months compared with 18.0 months in the SOC alone group (HR 1.07, 95% CI: 0.97, 1.18). The median time to progression (TTP) based on investigator-determined progressive disease (PD) was 7.5 months in the epoetin alfa plus SOC group and 7.5 months in the SOC group (HR 1.099, 95% CI: 0.998, 1.210). The median TTP based on IRC-determined PD was 8.0 months in the epoetin alfa plus SOC group and 8.3 months in the SOC group (HR 1.033, 95% CI: 0.924, 1.156).

 

In a prospective, randomised double‑blind, placebo‑controlled study conducted in 314 lung cancer patients receiving platinum containing chemotherapy there was a significant reduction in transfusion requirements (p < 0.001).

 

Clinical studies have demonstrated that darbepoetin alfa had similar effectiveness when administered as a single injection either once every three weeks, once every two weeks, or weekly without any increase in total dose requirements.

 

The safety and effectiveness of once every three weeks dosing of Aranesp therapy in reducing the requirement for red blood cell transfusions in patients undergoing chemotherapy was assessed in a randomised, double‑blind, multinational study. This study was conducted in 705 anaemic patients with non‑myeloid malignancies receiving multi‑cycle chemotherapy. Patients were randomised to receive Aranesp at 500 mcg once every three weeks or 2.25 mcg/kg once weekly. In both groups, the dose was reduced by 40% of the previous dose (e.g., for first dose reduction, to 300 mcg in the once every three weeks group and 1.35 mcg/kg in the once weekly group) if haemoglobin increased by more than 1 g/dL in a 14‑day period. In the once every three weeks group, 72% of patients required dose reductions. In the once weekly group, 75% of patients required dose reductions. This study supports 500 mcg once every three weeks being comparable to once weekly administration with respect to the incidence of subjects receiving at least one red blood cell transfusion from week 5 to the end of treatment phase.

 

In a prospective, randomised double‑blind, placebo‑controlled study conducted in 344 anaemic patients with lymphoproliferative malignancies receiving chemotherapy there was a significant reduction in transfusion requirements and an improvement in haemoglobin response (p < 0.001). Improvement in fatigue, as measured by the Functional Assessment of Cancer Therapy‑fatigue (FACT‑fatigue) scale, was also observed.

 

Erythropoietin is a growth factor that primarily stimulates red blood cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumour cells.

 

Survival and tumour progression have been examined in five large controlled studies involving a total of 2,833 patients, of which four were double‑blind placebo-controlled studies and one was an open‑label study. Two of the studies recruited patients who were being treated with chemotherapy. The target haemoglobin concentration in two studies was > 13 g/dL; in the remaining three studies it was 12‑14 g/dL. In the open‑label study there was no difference in overall survival between patients treated with recombinant human erythropoietin and controls. In the four placebo‑controlled studies the hazard ratios for overall survival ranged between 1.25 and 2.47 in favour of controls. These studies have shown a consistent unexplained statistically significant excess mortality in patients who have anaemia associated with various common cancers who received recombinant human erythropoietin compared to controls. Overall survival outcome in the trials could not be satisfactorily explained by differences in the incidence of thrombosis and related complications between those given recombinant human erythropoietin and those in the control group.

 

In a randomised, double-blind, placebo-controlled phase 3 study 2,549 adult patients with anaemia receiving chemotherapy for the treatment of advanced stage non-small cell lung cancer (NSCLC), were randomised 2:1 to darbepoetin alfa or placebo and treated to a maximum Hb of 12 g/dL. The results showed non-inferiority for the primary endpoint of overall survival with a median survival for darbepoetin alfa versus placebo of 9.5 and 9.3 months, respectively (stratified HR 0.92; 95% CI: 0.83–1.01). The secondary endpoint of progression free survival was 4.8 and 4.3 months, respectively (stratified HR 0.95; 95% CI: 0.87–1.04), ruling out the pre-defined 15% risk increase.

 

A systematic review has also been performed involving more than 9,000 cancer patients participating in 57 clinical trials. Meta‑analysis of overall survival data produced a hazard ratio point estimate of 1.08 in favour of controls (95% CI: 0.99, 1.18; 42 trials and 8,167 patients).

 

An increased relative risk of thromboembolic events (RR 1.67, 95% CI: 1.35, 2.06; 35 trials and 6,769 patients) was observed in patients treated with recombinant human erythropoietin. There is therefore consistent evidence to suggest that there may be significant harm to patients with cancer who are treated with recombinant human erythropoietin. The extent to which these outcomes might apply to the administration of recombinant human erythropoietin to patients with cancer, treated with chemotherapy to achieve haemoglobin concentrations less than 13 g/dL, is unclear because few patients with these characteristics were included in the data reviewed.

 

A patient‑level data analysis has also been performed on more than 13,900 cancer patients (chemo‑, radio‑, chemoradio‑, or no therapy) participating in 53 controlled clinical trials involving several epoetins. Meta‑analysis of overall survival data produced a hazard ratio point estimate of 1.06 in favour of controls (95% CI: 1.00, 1.12; 53 trials and 13,933 patients) and for the cancer patients receiving chemotherapy, the overall survival hazard ratio was 1.04 (95% CI: 0.97, 1.11; 38 trials and 10,441 patients). Meta‑analyses also indicate consistently a significantly increased relative risk of thromboembolic events in cancer patients receiving recombinant human erythropoietin (see section 4.4).

 


Due to its increased carbohydrate content the level of darbepoetin alfa in the circulation remains above the minimum stimulatory concentration for erythropoiesis for longer than the equivalent molar dose of r‑HuEPO, allowing darbepoetin alfa to be administered less frequently to achieve the same biological response.

 

Chronic renal failure patients

 

The pharmacokinetics of darbepoetin alfa has been studied clinically in chronic renal failure patients following intravenous and subcutaneous administration. The terminal half‑life of darbepoetin alfa is 21 hours (SD 7.5) when administered intravenously. Clearance of darbepoetin alfa is 1.9 mL/hr/kg (SD 0.56) and the volume of distribution (Vss) is approximately equal to plasma volume (50 mL/kg). Bioavailability is 37% with subcutaneous administration. Following monthly administration of darbepoetin alfa, at subcutaneous doses ranging from 0.6 to 2.1 mcg/kg, the terminal half‑life was 73 hours (SD 24). The longer terminal half‑life of darbepoetin alfa administered subcutaneously compared to intravenously is due to subcutaneous absorption kinetics. In clinical studies, minimal accumulation was observed with either route of administration. In preclinical studies it has been shown that renal clearance is minimal (up to 2% of total clearance), and does not affect the serum half‑life.

 

Data from 809 patients receiving Aranesp in European clinical studies were analysed to assess the dose required to maintain haemoglobin; no difference was observed between the average weekly dose administered via the intravenous or subcutaneous routes of injection.

 

The pharmacokinetics of darbepoetin alfa in paediatric patients (2 to 16 years) with CRF who were either receiving or not receiving dialysis was assessed for sampling periods up to 2 weeks (336 hours) after one or two subcutaneous or intravenous doses. Where the same sampling duration was used, observed pharmacokinetic data and population pharmacokinetic modelling demonstrated that the pharmacokinetics of darbepoetin alfa was similar for paediatric and adult patients with CRF.

 

In a phase 1 pharmacokinetic study, following intravenous administration, an approximate 25% difference between paediatric and adult patients in the area under the curve from time 0 to infinity (AUC[0‑∞]) was observed; however, this difference was less than the 2‑fold range in AUC(0-∞) observed for the paediatric patients. AUC(0‑∞) was similar between adult and paediatric patients with CRF following subcutaneous administration. Half-life was also similar between adult and paediatric patients with CRF following both intravenous and subcutaneous administration.

 

Cancer patients receiving chemotherapy

 

Following subcutaneous administration of 2.25 mcg/kg to adult cancer patients a mean peak concentration of 10.6 ng/mL (SD 5.9) of darbepoetin alfa was reached at a mean time of 91 hours (SD 19.7). These parameters were consistent with dose linear pharmacokinetics over a wide dose range (0.5 to 8 mcg/kg weekly and 3 to 9 mcg/kg every two weeks). Pharmacokinetic parameters did not change on multiple dosing over 12 weeks (dosing every week or every two weeks). There was an expected moderate (< 2 fold) increase in serum concentration as steady state was approached, but no unexpected accumulation upon repeated administration. A pharmacokinetic study in patients with chemotherapy‑induced anaemia treated with 6.75 mcg/kg darbepoetin alfa administered SC every 3 weeks in combination with chemotherapy was conducted which allowed for full characterisation of the terminal half‑life. In this study, mean (SD) terminal half‑life was 74 (SD 27) hours.


 

In all studies in rats and dogs darbepoetin alfa produced marked increases in haemoglobin, haematocrits, red blood cell counts and reticulocytes, which correspond to the expected pharmacological effects. Adverse events at very high doses were all considered to be related to an exaggerated pharmacological effect (decreased tissue perfusion due to increased blood viscosity). These included myelofibrosis and splenic hypertrophy as well as broadening of the ECG‑QRS complex in dogs but no dysrhythmia and no effect on the QT interval were observed.

 

Darbepoetin alfa did not reveal any genotoxic potential nor did it have any effect on the proliferation of non‑haematological cells in vitro or in vivo. In the chronic toxicity studies no tumourigenic or unexpected mitogenic responses were observed in any tissue type. The carcinogenic potential of darbepoetin alfa has not been evaluated in long‑term animal studies.

 

In studies performed in rats and rabbits no clinically relevant evidence of harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development was observed. Placental transfer was minimal. No alteration of fertility was detected.

 


Each 1 mL contains:

Polysorbate 80 (0.05 mg);

Sodium phosphate monobasic monohydrate (2.12 mg);

Sodium phosphate dibasic anhydrous (0.66 mg);

Sodium chloride (8.18 mg);

in Water for Injection, USP (up to 1 mL).


In the absence of incompatibility studies, this medicinal product must not be mixed or administered as an infusion with other medicinal products.

 


3 years.

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

 

For the purpose of ambulatory use, Aranesp may be removed from storage once for a maximum single period of seven days at room temperature (up to 25°C). Once a syringe has been removed from the refrigerator and has reached room temperature (up to 25°C) it must either be used within 7 days or disposed of.

 


Not all pack sizes may be marketed.

 

0.4 mL solution for injection (25 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.5 mL solution for injection (40 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.3 mL solution for injection (100 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.4 mL solution for injection (100 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.5 mL solution for injection (100 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.3 mL solution for injection (200 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.4 mL solution for injection (200 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.5 mL solution for injection (200 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.3 mL solution for injection (500 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

0.6 mL solution for injection (500 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

1 mL solution for injection (500 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre‑filled syringes.

 

The syringes may be presented in either blistered (1- and 4-pack), with or without an automatic needle guard or non‑blistered packaging (1-pack only).

 

The needle cap of the pre-filled syringe contains dry natural rubber (a derivative of latex). See section 4.4.

 


The carton contains a package leaflet with the full instructions for use and handling.

 

Aranesp is a sterile but unpreserved product. Do not administer more than one dose. Any medicinal product remaining in the pre-filled syringe should be disposed of.

Before administration the Aranesp solution should be inspected for visible particles. Only solutions which are colourless, clear or slightly opalescent, should be injected. Do not shake. Allow the pre‑filled syringe to reach room temperature before injecting.

 

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

 


Amgen Europe B.V. Minervum 7061 4817 ZK Breda The Netherlands

November 2019
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