برجاء الإنتظار ...

Search Results



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)

Epirubicin “Ebewe” belongs to the therapeutic group of antineoplastic agents (medicine against cancer).

 

Epirubicin “Ebewe” is used to treat different types of cancer, i.e.:

·       Breast cancer

·       Stomach cancer

 

Epirubicin “Ebewe” is also used to help prevent recurrence of bladder after surgery.

It is used either alone or in combination with other anti-cancer medicines.


 Do not use Epirubicin “Ebewe”:

·         if you are allergic to epirubicin hydrochloride or any of the other ingredients of this medicine (listed in section 6), or similar medicines on previous occasions

  • if you have fewer blood cells than normal (your doctor will check this)
  • if you have been treated with high doses of some other anti-cancer medicines including doxorubicin and daunorubicin which belong to the same group of drugs as epirubicin hydrochloride (called anthracyclines). These medicines have similar side effects (including those effects on the heart).
  • if you have suffered or currently have problems with your heart
  • if you have severe liver problems
  • if you have a severe  infection
  • if you are experiencing severe inflammation or ulcers in your mouth and gastro-intestinal tract.

 

 

For instillation into the bladder, Epirubicin “Ebewe” should not be used

  • if your tumour penetrates the bladder wall
  • if you have a urine infection
  • if you have inflammation of your bladder
  • if your doctor has problems inserting a catheter (tube) in your bladder
  • if there is a large volume of urine left in your bladder after you attempt to empty it.
  • if you have a contracted bladder.
  • if you have blood in the urine

 

Warnings and precautions

Special care will be taken:

  • to ensure the numbers of white and red blood cells and platelets do not drop too low. Your doctor will regularly check this.
  • to check the level of uric acid in your blood. Your doctor will check this.
  • if you have liver disease
  • if you have kidney disease
  • if you have an unstable angina pectoris
  • to ensure your heart is working properly. Your doctor will regularly check this.

if you have received or are receiving radiotherapy to the chest area

 

 

Other medicines and Epirubicin “Ebewe”

Special care is needed if you are taking/using other medicines as some could interact with epirubicin.

These medicines include:

·         other medicines that may affect your heart for example; calcium channel blockers (e.g. verapamil, nifedipine and diltiazem), other cancer treatments such as doxorubicin, mitomycin‑C, dacarbazine, dactinomycin and possibly cyclophosphamide and radiotherapy

·         other medicines that may affect your liver e.g. barbiturates (medicines used in epilepsy or sleep disorders) and rifampicin (a medicine used to treat TB)

·         trastuzumab; epirubicin should not be taken within 27 weeks of taking trastuzumab

·         cimetidine (a medicine used to reduce the acid in your stomach)

·         paclitaxel and docetaxel (medicines used in some cancers)

·         interferon alfa-2b (a medicine used in some cancers and lymphomas and for some forms of hepatitis)

·         quinine (medicine used for treatment of malaria and for leg cramps)

·         dexrazoxane (a medicine sometimes used with doxorubicin to reduce the risk of heart problems)

·         dexverapamil (a medicine used to treat some heart conditions).

 

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

 

If you need to have any vaccinations, you must inform your doctor that you are being treated with epirubicin before receiving the vaccination as certain types of vaccines (live and live-attenuated) may have serious side effects.

 

Pregnancy, breast-feeding and fertility

 

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

 

Due to the risk of birth defects, women of childbearing potential should use appropriate contraception methods during treatment with epirubicin. Male patients are advised not to father a child during and for 6-months after stopping epirubicin treatment

 

You must not breast feed if you are taking epirubicin.

 

Male patients may wish to seek advice on sperm preservation before treatment starts and should use effective contraceptive methods during treatment.

 

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

Epirubicin “Ebewe” driving and using machines

No studies on the effects on the ability to drive and use machines have been performed with epirubicin. However, epirubicin may cause nausea and vomiting, which can temporarily affect your ability to drive and use machines.

                         

 Epirubicin “Ebewe” contains sodium.

This medicinal product contains 0.154 mmol/ml (3.54 mg/ml) sodium.

1 vial of 5 ml solution contains 0.77 mmol (17.70 mg) sodium.

1 vial of 25 ml solution contains 3.85 mmol (88.52 mg) sodium.

1 vial of 50 ml solution contains 7.70 mmol (177.02 mg) sodium.

1 vial of 100 ml solution contains 15.40 mmol (354.05 mg) sodium.

 

Doses below 10 ml: This medicinal product contains less than 1mmol sodium (22 mg) per dose, i. e. it is essentially sodiumfree.

Doses of 10 ml and above: This medicinal product contains 0.077 mmol/ml. This should be taken into consideration by patients on a controlled sodium diet.

 


Epirubicin “Ebewe” will only be given to you under supervision of a doctor specialised in this type of treatment. Before and during treatment with Epirubicin “Ebewe”, your doctor will check various laboratory parameters (e.g. blood cell count, blood uric acid level, your liver function) and carefully monitor your heart function. Monitoring of the heart function will be continued for several weeks following the end of treatment with Epirubicin “Ebewe””.

 

When given by injection or infusion into a vein

Each dose of Epirubicin “Ebewe” is based on your body surface area. This is calculated from your height and weight. The dose of  Epirubicin “Ebewe” given to you will also depend on the type of cancer you have, your health, how well your liver or kidney is working and any other medicines you may be taking.

 

When given as a single agent, the usual dose of epirubicin hydrochloride is 60-90 mg/m2 body surface area. Higher dosages (100-120 mg/m2 body surface area) may be given to you if you suffer from breast cancer.

 

Dosage will be reduced or the following dose could be delayed if you have a low level of white blood cells in your body, if you are elderly, if you have liver problems, or if the drug is used in combination with other anticancer drugs.

 

Epirubicin “Ebewe” may be given as an injection into a vein over 3-5 minutes. It may also be diluted with glucose (sugar solution) or sodium chloride (salt water) before it is infused slowly, usually via a drip into a vein over 30 minutes. Usually it will be given to you every 3 (or 4) weeks.

 

The needle must remain in the vein while Epirubicin “Ebewe” is being given. If the needle comes out or becomes loose, or the solution is going into the tissue outside the vein (you may feel discomfort or pain) - tell the doctor or nurse immediately.

 

When given directly into the bladder (intravesical administration)

The medicine may be given directly into the bladder using a catheter. If this route is used, you should not drink any fluids for 12 hours before treatment so that your urine will not dilute the drug too much.

 

The dose will depend upon the type of bladder cancer.

 

The solution should be kept in your bladder for 1-2 hours after instillation. You will be rotated occasionally to ensure even exposure of all parts of the bladder to the drug.

 

Care should be taken to ensure that the contents of the bladder, when emptied, do not come into contact with the skin. In case of skin contact, thoroughly wash the affected area with soap and water but do not scrub.

 

If you received more Epirubicin “Ebewe” than you should

As this medicine will be given to you whilst you are in hospital it is unlikely that you will be given too much, however, tell your doctor or pharmacist if you have any concerns.

 

If you missed a dose of  Epirubicin “Ebewe”

Epirubicin “Ebewe” needs to be given on a fixed schedule. Be sure to keep all appointments. If you miss a dose, you should discuss this with your doctor. Your doctor will decide when you should be given your next dose of Epirubicin “Ebewe”.

 

If you stop treatment with Epirubicin “Ebewe”

Stopping your treatment with Epirubicin “Ebewe” may stop the effect on tumour growth. Do not stop treatment with Epirubicin “Ebewe” unless you have discussed this with your doctor.

 

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


Like all medicines, Epirubicin “Ebewe” can cause side effects, although not everybody gets them. If you experience any of the following side effects when epirubicin is given by infusion into a vein, tell your doctor immediately as these are all serious. You may need urgent medical attention or hospitalisation:

·                     if there is any redness, pain or swelling at the injection site

·                     you have symptoms of heart problems such as chest pain, shortness of breath, swelling of your ankles (these effects may occur up to several weeks after finishing treatment with Epirubicin “Ebewe”)

·                     If you have a severe allergic reaction, symptoms include faintness, skin rash, itching, fever, chills, swelling of the face and difficulty in breathing of wheeze. In some cases collapse may occur.

           

Other side effects that may occur:

 

 

Very common, may affect more than 1 in 10 people:

·         inhibition of blood cell production in the bone marrow (myelosuppression)

·         decreased number of white blood cells (leucocytopenia)

·         decreased number of a special form of white blood cells (granulocytopenia and neutropenia)

·         neutropenia accompanied by fever (febrile neutropenia)

·         decrease in red blood cells (anaemia)

·         hair loss (alopecia) normally reversible

·         your urine may have a red colour for up to two days after treatment. This is normal and nothing to worry about

 

Common, may affect up to 1 in 10 people:

·         Feeling and being sick (nausea and vomiting)

·         Diarrhoea

·         feeling very dry and thirsty (dehydration)

·         Infection

·         Loss of appetite

·         inflammation of the oesophagus (oesophagitis)

·         Inflammation of the mouth

·         Hot flushes

·         inflammation of a mucous membrane (mucositis)

·         inflammation of the mucosa of the mouth with areas of painful erosions, ulceration and

bleeding (stomatitis)

·         Injection site reactions (eg. redness)

·         bladder inflammation with pain when passing urine (chemical cystitis), sometimes with blood

in the urine (haemorrhagic) following administration into the bladder

 

 

Uncommon, may affect up to 1 in 100 people:

·         Inflammation of the veins (phlebitis) which may be associated with blood clots (thrombophlebitis) - this may present as pain and/or swelling in your arms or legs

·         decreased number of platelets (thrombocytopenia)

 

 

Rare, may affect up to 1 in 1,000 people:

·         Dizziness

·         severe hypersensitivity (anaphylaxis)

·         Malaise and weakness,

·         Abnormal heart rhythm or rate; changes in the ECG (heart trace), congestive heart failure (with shortness of breath, fluid in the lungs and abdomen, swelling of the ankles and changes in heart rhythm).

·         Enlargement of the liver

·         Nettle rash (urticaria)

·         Lack of periods (amenorrhoea)

·         Reduced levels of sperm in males (azoospermia)

·         Feeling unusually hot or cold (fever or chills)

·         Leukaemia (acute lymphocytic or acute myelogenous) may occur up to 3 years after treatment

·         Raised blood uric acid levels ‑ which may be part of a syndrome associated with tumour breakdown. Your doctor will monitor you with blood tests

 

Not known, frequency cannot be estimated from the available data:

·         fever, infections, inflammation of the lungs (pneumonia), systemic infection (sepsis) or a state of shock resulting from blood poisoning (septic shock) may occur.

·         Bleeding (haemorrhage) and inadequate oxygen supply to tissues (tissue hypoxia) were reported as a result of reduced blood cell production in the bone marrow

·         discharge from the eye with itching, redness and swelling (conjunctivitis); eye pain, blurred vision, abnormal intolerance to light (keratitis)

·         occlusion of blood vessel due to a blood clot (thromboembolic events) including occlusion of a  blood vessel in the lungs (pulmonary embolism [in isolated cases with fatal outcome])

  • Inflammation, burning sensation and pain in the mouth, sores and pain on swallowing, pigmentations and bleedings in the mouth.
  • Local toxicity, rash, itch, skin changes, erythema, flushes, skin and nail hyperpigmentation, photosensitivity, hypersensitivity to irradiated skin (radiation-recall reaction)

·         hardening and loss of elasticity of the veins (phlebosklerosis), severe cellulitis, tissue necrosis after accidental paravenous injection

  • the quantity of blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction may be reduced (asymtomatic drops in left ventricular ejection fraction).

 

 

Side effects after epirubicin injection into the bladder

 

If epirubicin is injected directly into the bladder (intravesically), only a small amount is absorbed into the body so the side effects listed above are rare. However, inflammation and infection of the bladder may occur and you may experience discomfort, pain or difficulty when passing urine and blood may be seen in your urine. These side effects are mostly reversible. If you notice these side effects you should inform your doctor.

 

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

 


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 the vial after EXP. The expiry date refers to the last day of that month.

 

Store refrigerated (2°C to 8ºC).

 

Shelf life after dilution:

Chemical and physical in-use stability has been demonstrated for 7 days at 2 to 8°C in Glucose 5 % or Sodium Chloride 0.9 %.

In use: From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8ºC.

 

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

 


-                 The active substance is epirubicin hydrochloride.

-                 The other ingredients are sodium chloride, hydrochloric acid, water for injections.

 

Each milliliter (ml) of solution contains 2 mg of epirubicin hydrochloride.

 

5 ml vial: each vial contains 10 mg epirubicin hydrochloride.

25 ml vial: each vial contains 50 mg epirubicin hydrochloride.

50 ml vial: each vial contains 100 mg epirubicin hydrochloride.

100 ml vial: each vial contains 200 mg epirubicin hydrochloride.


The solution for injection and infusion is a clear, red solution. This medicinal product is a solution for injection. Packaging with 1 vial, 5 or 10 vials of 5 ml solution. Packaging with 1 vial, 5 or 10 vials of 25 ml solution. Packaging with 1 vial, 5 or 10 vials of 50 ml solution. Packaging with 1 vial, 5 or 10 vials of 100 ml solution. The vials may be overwrapped with a protective plastic (ONKO-SAFE). The ONKO-SAFE has no contact with the drug product and increases safety during transport for medical and pharmaceutical personnel. Not all pack sizes may be marketed.

Marketing Authorization Holder

EBEWE Pharma Ges.m.b.H. Nfg.KG A-4866 Unterach, AUSTRIA


04/2020
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

ينتمي عقار إيِبيِروبِيسين "إيبيفيه" إلى المجموعة العلاجية الخاصة بمضادات الأورام (دواء مضاد للسرطان).

 

يُستخدم عقار إيِبيِروبِيسين "إيبيفيه" لعلاج أنواع مختلفة من السرطان، أي:

·       سرطان الثدي.

·       سرطان المعدة.

 

يُستَخدَم عقار إيِبيِروبِيسين "إيبيفيه" أيضًا للمساعدة في الوقاية من تكرار حدوث سرطان المثانة بعد الجراحة.

يُستَخدَم إما وحده أو بمصاحبة مضادات السرطان الأخرى.

لا تستخدم عقار إيِبيِروبِيسين "إيبيفيه" في الحالات الآتية:

·         إذا كنت تعاني من حساسية تجاه إيِبيِروبِيسين هيدروكلوريد أو تجاه أي مكون من المكونات الأخرى بهذا الدَّواء (المدرجة في قسم: 6)، أو أدوية مماثلة في حالات سابقة

  • إذا كان لديك عدد خلايا الدَّم أقل من المستوى الطبيعي (سيفحص طبيبك هذا الأمر).
  • إذا عُولجت بجرعات مرتفعة من بعض مضادات السرطان الأخرى بما في ذلك دوكسوروبيسين وداونوروبيسين التي تنتمي إلى نفس مجموعة عقاقير إيِبيِروبِيسين هيدروكلوريد (تُسمى الأنثراسيكلينات). لهذه الأدوية آثار جانبية مماثلة (بما في ذلك الآثار على القلب).
  • إذا كنت قد عانيت أو تعاني حاليًا من مشاكل بالقلب.
  • إذا كان لديك مشاكل شديدة بالكبد.
  • إذا كنت تعاني من عدوى شديدة.
  • إذا كنت تُعاني من التهاب شديد أو قُرَح شديدة في فمك وجهازك الهضمي.

 

بالنسبة للتقطير في المثانة، يجب عدم استخدام عقار إيِبيِروبِيسين "إيبيفيه"

  • إذا اخترق الورم لديك جدار المثانة.
  • إذا كنت تُعاني من عدوى المسالك البولية.
  • إذا كنت تُعاني من التهاب في المثانة.
  • إذا كان طبيبك يواجه مشاكل في إدخال القسطرة (الأنبوب) في المثانة لديك.
  • إذا كان هناك كمية كبيرة من البول متبقية في المثانة بعد محاولتك إفراغها.
  • إذا كنت تُعاني من مَثانَة مُتَقَلِّصة.
  • إذا كان لديك دم في البول.

 

تحذيرات واحتياطات

سيتم إيلاء عناية خاصة:

  • لضمان عدم حدوث انخفاض شديد في تعداد خلايا الدَّم الحمراء والبيضاء والصفائح الدَّموية. سيقوم طبيبك بفحص ذلك بصفة منتظمة.
  • لفحص مستوى حمض اليوريك في دمك. سيقوم طبيبك بفحص ذلك.
  • إذا كان لديك مرض بالكبد.
  • إذا كان لديك مرض بالكُلى.
  • إذا كنت تعاني من ذبحة صدرية غير مستقرة.
  • للتأكد من أنَّ قلبك يعمل بشكل سليم. سيقوم طبيبك بفحص ذلك بصفة منتظمة.

إذا تلقيت أو كنت تتلقى علاجًا إشعاعيًّا في منطقة الصدر.

 

 

الأدوية الأخرى وعقار إيِبيِروبِيسين "إيبيفيه"

يجب إيلاء عناية خاصة إذا كنت تتناول/ تستخدم أدوية أخرى لأنَّ بعضها قد يتداخل مع عقار إيِبيِروبِيسين.

وتشمل هذه الأدوية:

·         الأدوية الأخرى التي قد تُؤثر على قلبك، على سبيل المثال: حاصرات قنوات الكالسيوم (على سبيل المثال: فيراباميل ونيفيديبين وديلتِيازِيم)، علاجات السرطان الأخرى مثل: دوكسوروبيسين، ميتوميسين سي، داكاربازين، داكتينومايسين وربما سيكلوفوسفاميد والعلاج الإشعاعي.

·         الأدوية الأخرى التي قد تُؤثر على الكبد لديك، على سبيل المثال: الباربيتورات (أدوية تُستَخدَم في علاج الصَّرَع أو اضطراباب النوم) وريفامبيسين (دواء يُستَخدَم لعلاج مرض السُّل).

·         تراستوزوماب؛ يجب ألا يتم تناوُل عقار إيِبيِروبِيسين في غضون 27 أسبوعًا من تناوُل تراستوزوماب.

·         سيميتيدين (دواء يُستَخدَم لخفض الحمض في المعدة لديك).

·         باكليتاكسيل ودوسيتاكسيل (أدوية تُستَخدَم في علاج بعض السرطانات).

·         إنترفيرون ألفا-2ب (دواء يُستَخدَم في علاج بعض السرطانات وأورام الغدد الليمفاوية وبعض أشكال التهاب الكبد).

·         كينين (دواء يُستَخدَم لعلاج الملاريا وتقلصُّات عضلات الساق).

·         ديكسرازوكسون (دواء يُستَخدَم في بعض الأحيان مع دوكسوروبيسين لتقليل خطر الإصابة بمشاكل في القلب).

·         ديكسفيراباميل (دواء يُستَخدَم لعلاج بعض حالات القلب).

 

يُرجى إبلاغ طبيبك إذا كنت تتناول أو تناولت مؤخرًا أو قد تتناول أيَّة أدوية أخرى.

 

إذا احتجت إلى تلقي أيَّة لقاحات، فيجب عليك إبلاغ طبيبك بأنك تُعالَج بعقار إيِبيِروبِيسين قبل تلقي اللقاح؛ وذلك لأنَّ بعض أنواع اللقاحات (الحية والحية المُوهِنة) قد يكون لها آثار جانبية خطيرة.

 

الحمل والرَّضاعة الطبيعية والخصوبة

 

إذا كنتِ حاملًا أو مرضعًا، أو تعتقدين أنكِ حامل أو تخططين لذلك، فاستشيري طبيبكِ قبل تناوُل هذا الدَّواء. وسيقرر طبيبكِ ما إذا كان ينبغي عليكِ تلقي هذا الدَّواء أم لا.

 

نظرًا لخطر الإصابة بعيوب خلقية، يجب على السيدات ممن لديهن القدرة على الحَمْل استخدام وسائل مناسبة لمنع الحَمْل أثناء العلاج بعقار إيِبيِروبِيسين.يُنصَح المرضى من الذكور بعدم الإنجاب أثناء العلاج ولمدة 6 أشهر بعد التَّوقف عن العلاج بعقار إيِبيِروبِيسين.

 

يجب أَلَّا تمارسي الرضاعة الطبيعية إذا كنتِ تتناولين عقار إيِبيِروبِيسين.

 

قد يرغب المرضى من الذكور في طلب المشورة بشأن حفظ حيواناتهم المنوية قبل بدء العلاج كما أن عليهم استخدام وسائل فعَّالة لمنع الحَمْل أثناء العلاج.

 

استشيري طبيبكِ أو الصيدلي قبل استخدام هذا الدَّواء.

عقار إيِبيِروبِيسين "إيبيفيه" القيادة واستخدام الآلات

لم يتم إجراء أيَّة دراسات بشأن التَّأثيرات في القدرة على القيادة واستخدام الآلات مع عقار إيِبيِروبِيسين. مع ذلك، قد يُسبب عقار إيِبيِروبِيسين الغثيان والقيء، وهو ما قد يُؤثر مؤقتًا في قدرتك على قيادة المركبات واستخدام الآلات.

                         

 يحتوي عقار إيِبيِروبِيسين "إيبيفيه" على الصوديوم.

يحتوي هذا المُنتَج الدَّوائي على 0.154 مللي مول/ مللي لتر (3.54 مجم/ مللي لتر) من الصوديوم.

تحتوي الزجاجة الواحدة التي تحتوي على 5 مللي لتر من المحلول على 0.77 مللي مول (17.70 مجم) من الصوديوم.

تحتوي الزجاجة الواحدة التي تحتوي على 25 مللي لتر من المحلول على 3.85 مللي مول (88.52 مجم) من الصوديوم.

تحتوي الزجاجة الواحدة التي تحتوي على 50 مللي لتر من المحلول على 7.70 مللي مول (177.02 مجم) من الصوديوم.

تحتوي الزجاجة الواحدة التي تحتوي على 100 مللي لتر من المحلول على 15.40 مللي مول (354.05 مجم) من الصوديوم.

 

الجرعات الأقل من 10 مللي لتر: يحتوي هذا المنتج الدَّوائي على أقل من 1 مللي مول صوديوم (22 مجم) لكل جرعة، أي أنه خالٍ من الصوديوم بشكل أساسي.

الجرعات التي تبلغ 10 مللي لتر فأكثر: يحتوي هذا المنتج الدَّوائي على 0.077 مللي مول/ مللي لتر. يجب أخذ ذلك في الاعتبار من قبل المرضى الذين يتبعون نظامًا غذائيًّا منخفض الصوديوم (الملح).

 

https://localhost:44358/Dashboard

سيتم إعطاؤك عقار إيِبيِروبِيسين إيبيفيه فقط تحت إشراف طبيب مُتخصص في هذا النوع من العلاج. سيقوم طبيبك قبل وأثناء العلاج بعقار إيِبيِروبِيسين "إيبيفيه" بفحص المُعامِلات المعملية المختلفة (على سبيل المثال: تعداد خلايا الدَّم، مستوى حمض اليوريك في الدَّم، وظائف الكبد لديك) وسيراقب بعناية وظائف القلب. ستتم مواصلة مراقبة وظائف القلب لعدة أسابيع بعد انتهاء العلاج بعقار إيِبيِروبِيسين "إيبيفيه".

 

عند إعطائه عن طريق الحَقْن أو التَّسريب في الوريد

تعتمد كل جرعة من عقار إيِبيِروبِيسين "إيبيفيه" على مساحة سطح الجسم لديك. ويتم حساب ذلك من خلال قياس طولك ووزنك. ستعتمد أيضًا جرعة عقار إيِبيِروبِيسين "إيبيفيه" المُعطاة لك على نوع السرطان الذي تُعاني منه، حالتك الصحية، مدى كفاءة عمل الكبد أو الكُلى لديك وأيَّة أدوية أخرى قد تكون تتناولها.

 

عند إعطائه كعقار مفرد، تكون الجرعة المُعتادة من إيِبيِروبِيسين هيدروكلوريد 60-90 مجم/ متر مربع من مساحة سطح الجسم. قد يتم إعطاؤكِ جرعات أعلى (100-120 مجم/ متر مربع من مساحة سطح الجسم) إذا كنتِ تُعانين من سرطان الثدي.

 

سيتم خفض الجرعة أو قد يتم تأخير الجرعة التَّالية إذا كان مستوى خلايا الدَّم البيضاء في جسمك منخفضًا أو إذا كنت من كبار السن أو إذا كنت تُعاني من مشاكل في الكبد أو إذا كنت تستخدم العقار بمصاحبة عقاقير أخرى مضادة لمرض السرطان.

 

قد يتم إعطاء عقار إيِبيِروبِيسين "إيبيفيه" في هيئة حَقْن في الوريد على مدار 3-5 دقائق. يُمكِن تخفيفه أيضًا بالجلوكوز (محلول السكر) أو كلوريد الصوديوم (ماء مملح) قبل تسريبه ببطء، عادةً عن طريق التَّسريب بالتَّنقيط في الوريد على مدار 30 دقيقة. عادةً سيتم إعطاؤه لك كل 3 (أو 4) أسابيع.

 

يجب أن تبقى الإبرة في الوريد أثناء إعطاء عقار إيِبيِروبِيسين "إيبيفيه". إذا خرجت الإبرة أو أصبحت غير مثبتة بإحكام، أو إذا دخل المحلول في نسيج خارج الوريد (قد تشعر بالانزعاج أو الألم) - فأخبِر الطبيب أو الممرض(ة) فورًا.

 

عند إعطائه مباشرةً في المثانة (الإعطاء داخل المثانة).

قد يتم إعطاء الدَّواء مباشرةً في المثانة باستخدام القسطرة. إذا تم استخدام هذا الطريق (أي المثانة)، فيجب ألا تشرب أي سوائل لمدة 12 ساعة قبل العلاج بحيث لا يخفف البول من تركيز العقار بشكل كبير.

 

ستعتمد الجرعة على نوع سرطان المثانة الذي تُعاني منه.

 

يجب إبقاء المحلول في المثانة لمدة 1-2 ساعة بعد التَّقطير. سيتم تغيير موضعك من حين لآخر؛ لضمان تعرُّض جميع أجزاء المثانة للعقار بشكل متساوٍ.

 

يجب توخي الحذر؛ لضمان أنَّ محتويات المثانة -عند إفراغها- لا تتلامس مع الجلد. في حال ملامسة الجلد، اغسل المنطقة المتأثرة جيدًا بالماء والصابون ولكن لا تفركها.

 

إذا تلقيت كمية أكبر مما يجب من عقار إيِبيِروبِيسين "إيبيفيه"

نظرًا إلى أنَّ هذا الدَّواء سيتم إعطاؤه لك أثناء وجودك في المستشفى، فمن غير المُحتَمل أن تتلقى كمية أكثر مما يجب، ولكن أخبِر طبيبك أو الصيدلي الخاص بك إذا كانت لديك أيَّة مخاوف.

 

إذا أغفلت جرعة من عقار إيِبيِروبِيسين "إيبيفيه"

ينبغي إعطاء عقار إيِبيِروبِيسين "إيبيفيه" طبقًا لجدول مواعيد ثابت. تأكَّد من الحفاظ على جميع المواعيد إذا أغفلت تناول إحدى الجرعات،يجب مناقشة ذلك مع طبيبك. سيقرر طبيبك متى يجب إعطاؤك الجرعة التَّالية من عقار إيِبيِروبِيسين "إيبيفيه".

 

إذا توقفت عن العلاج بعقار إيِبيِروبِيسين "إيبيفيه"

إيقاف علاجك بعقار إيِبيِروبِيسين "إيبيفيه" من شأنه أن يوقف التَّأثير على نمو الورم. ينبغي أَلَّا توقف العلاج بعقار إيِبيِروبِيسين "إيبيفيه" إلا إذا ناقشت هذا الأمر مع طبيبك.

 

إذا كانت لديك أية أسئلة إضافية حول استخدام هذا المنتج، فاستشر طبيبك أو الصيدلي.

مثله مثل كافة الأدوية، قد يُسبب عقار إيِبيِروبِيسين "إيبيفيه" آثارًا جانبية، على الرَّغم من عدم حدوثها لدى الجميع.  إذا تعرَّضت لأي من الآثار الجانبية التَّالية عند إعطاء عقار إيِبيِروبِيسين لك عن طريق التَّسريب في الوريد، فأخبر طبيبك فورًا؛ نظرًا لخطورة هذه الآثار جميعها. قد تحتاج إلى رعاية طبية عاجلة أو دخول المستشفى.

·                     إذا تعرَّضت لأي احمرار أو ألم أو تورُّم في موضع الحَقْن.

·                     إذا كان لديك أعراض تُشير إلى مشاكل في القلب مثل ألم في الصدر، ضيق بالتَّنفس، تورُّم الكاحلين (قد تحدث هذه الآثار بعد ما يصل إلى عدة أسابيع من الانتهاء من العلاج بعقار إيِبيِروبِيسين "إيبيفيه").

·                     إذا كانت لديك تفاعلات حساسية شديدة، تشمل الأعراض: الإصابة بإغماء، طفحًا جلديًّا، حكة، حُمّى، ارتعاشًا، تورُّم الوجه وصعوبة في التَّنفس بسبب أزيز الصدر. في بعض الحالات قد يحدث هبوط.

 

الآثار الجانبية الأخرى التي قد تحدث:

 

شائعة جدًّا،  قد تُؤثر على أكثر من 1 من بين كل 10 أشخاص:

·         تثبيط إنتاج خلايا الدَّم في النخاع العظمي (كبت النخاع العظمي).

·         انخفاض عدد خلايا الدَّم البيضاء (قلة خلايا الدَّم البيضاء).

·         انخفاض عدد أحد أشكال خلايا الدَّم البيضاء (قلة خلايا المحببات وقلة خلايا العَدِلات).

·         قلة خلايا العَدِلات المصحوبة بحُمّى (قلة خلايا العَدِلات الحُمّوي).

·         انخفاض في خلايا الدَّم الحمراء (فقر الدم (أنيميا)).

·         تساقط الشعر (الثعلبة)، عادة قابل للارتداد.

·         قد يكتسب البول لونًا أحمر لمدة تصل إلى يومين بعد العلاج. هذا الأمر طبيعي ولا يدعو للقلق.

 

شائعة، قد تُؤثر على ما يصل إلى شخص واحد من كل ١٠ أشخاص:

·         شعور بالإعياء والإعياء (الغثيان والقيء).

·         إِسْهال.

·         شعور بجفاف شديد وعطش (جفاف).

·         عدوى.

·         فقدان الشهية.

·         التهاب المريء.

·         التهاب الفم.

·         هبات ساخنة.

·         التهاب أحد الأغشية المخاطية.

·         التهاب غشاء الفم مع التعرُّض في بعض المواضع لتآكل مؤلم وتقرُّح ونزيف (التهاب الفم).

·         تفاعلات بموضع الحقن (على سبيل المثال: احمرار).

·         التهاب المثانة مع ألم عند التبوُّل (التهاب المثانة الكيميائي)، مع وجود دم في البول أحيانًا (نزيف) بعد إعطاء العقار في المثانة.

 

 

غير شائعة، قد تُؤثر على ما يصل إلى شخص واحد من بين كل ١٠٠ شخص:

·         التهاب الأوردة الذي قد تُصاحِبه جلطات دموية (التهاب الوريد الخثاري) - قد يظهر ذلك في هيئة ألم و/أو تورُّم في الذراعين أو الساقين.

·         انخفاض في عدد صفائح الدَّم (قلة الصفائح الدَّموية).

 

 

نادرة، قد تُؤثر على ما يصل إلى شخص واحد من بين كل ١٠٠٠ شخص:

·         دوخة

·         فرط الحساسية الشديد (التَّأق).

·         تَوَعُّك وضعف.

·         اضطراب في النَّظْم القلبي أو مُعدَّل ضربات القلب؛ تغيُّرات في رسم القلب الكهربائي، فشل القلب الاحتقاني (مع ضيق بالتَّنفس، سائل في الرئتين والبطن، تورُّم الكاحلين وتغيُّرات في النَّظْم القلبي).

·         تَضخُّم الكبد.

·         طفح القراص (أرتكاريا).

·         انقطاع دورات الحيض.

·         انخفاض مستويات الحيوانات المنوية لدى الذكور (فَقْد النِّطاف).

·         شعور بسخونة أو برودة غير مُعتادة (حُمّى أو ارتعاش).

·         قد يحدث سرطان الدَّم (سرطان الدَّم الليمفاوي الحاد أو سرطان الدَّم النقوي الحاد) بعد ما يصل إلى 3 سنوات من تلقي العلاج.

·         ارتفاع مستويات حمض اليوريك في الدَّم -والذي قد يكون جزءًا من متلازمة مصاحبة لانحلال الورم. سيراقب طبيبك حالتك مع إجراء اختبارات الدَّم.

 

غير معروفة، لا يمكن تقدير معدل التكرار من واقع البيانات المتاحة:

·         قد تحدث حُمّى، عدوى، التهاب الرئتين، عدوى جهازية (تعفُّن الدَّم) أو حالة من الصدمة نتيجة تسمم الدَّم (صدمة تعفُّن الدَّم).

·         تم الإبلاغ عن التعرُّض لنزيف ونقص إمداد الأكسجين إلى الأنسجة (نقص الأكسجين بالأنسجة) نتيجة انخفاض إنتاج خلايا الدَّم في النخاع العظمي.

·         إفرازات من العين مع حكة واحمرار وتورم (التهاب الملتحمة)؛ ألم بالعين، عدم وضوح الرؤية، عدم تحمل الضوء بشكل غير طبيعي (التهاب القرنية).

·         انسداد الأوعية الدَّموية بسبب تجلُّط الدَّم (أحداث الانصمام الخُثاري) بما في ذلك انسداد أحد الأوعية الدَّموية في الرئتين (انصمام رئوي [في حالات فردية ونتج عنه حالات وفاة]).

  • التهاب، إحساس بالحُرقة والألم في الفم، تقرحات وألم عند البلع، تصبُّغات وحالات نزيف في الفم.
  • تسمم موضعي، طفح جلدي، حكة، تغيُّرات بالجلد، حُمامي، احمرار، فرط تصبُّغ الجلد والأظافر، حساسية تجاه الضوء، فرط حساسية تجاه الجلد المُتعرِّض للإشعاع (تفاعل ارتدادي للإشعاع).

·         تصلب وفقدان مرونة الأوردة (تصلُّب الوريد)، الْتِهاب النّسِيجِ الخلوي الشديد، نخر النسيج بعد الحَقْن العَرَضي المجاور للوريد.

  • قد تنخفض كمية الدَّم الذي يتم ضخه من البطين الأيسر بالقلب (غرفة الضخ الأساسية) مع كل انقباض (حالات هبوط غير مصحوبة بأعراض في الكسر القذفي للبطين الأيسر).

 

 

الآثار الجانبية بعد حَقْن عقار إيِبيِروبِيسين في المثانة

 

إذا تم حَقْن عقار إيِبيِروبِيسين مباشرةً في المثانة، يتم امتصاص كمية قليلة فقط في الجسم؛ ولذلك فإنَّ الآثار الجانبية المُدرَجة أعلاه تُعَد نادرة الحدوث. ومع ذلك، قد يحدث التهاب وعدوى بالمثانة وقد تتعرَّض للشعور بضيق أو الألم أو مواجهة صعوبة عند التبوُّل وقد يُلاحَظ وجود دم في البول لديك. تكون هذه الآثار الجانبية في الأغلب قابلة للارتداد. إذا لاحظت هذه الآثار الجانبية فيجب عليك إبلاغ طبيبك.

 

 

إذا أُصبت بأية آثار جانبية، فتحدَّث إلى طبيبك أو الصيدلي أو الممرض(ة). ويشمل ذلك أية آثار جانبية غير المدرجة في هذه النَّشرة.

يُحفظ هذا الدَّواء بعيدًا عن رؤية ومتناول الأطفال.

 

لا تستعمل هذا الدَّواء بعد انتهاء تاريخ الصلاحية المدون على العبوة الكرتونية والزجاجة بعد كلمة "EXP".يُشير تاريخ انتهاء الصَّلاحية إلى اليوم الأخير من ذلك الشهر.

 

يحفظ في الثلاجة (عند 2—8 درجة مئوية).

 

عمر التَّخزين بعد التَّخفيف:

تم إثبات الاستقرار الكيميائي والفيزيائي أثناء الاستخدام لمدة 7 أيام عند 2-8 درجة مئوية وفي محلول جلوكوز 5٪ أو كلوريد الصوديوم 0.9٪.

أثناء الاستخدام: من وجهة النَّظر الميكروبيولوجية، يجب استخدام هذا المنتج فورًا. إذا لم يستخدم على الفور، تكون مدة التخزين أثناء الاستخدام وظروف التَّخزين قبل الاستخدام مسؤولية المستخدم وعادة لن تكون أطول من 24 ساعة عند درجة حرارة 2 - 8 درجة مئوية.

 

لا تتخلص من الأدوية عن طريق إلقائها في مياه الصرف أو مع المخلفات المنزلية. استشر الصيدلي الخاص بك عن كيفية التَّخلص من الأدوية التي لم تَعد تستخدمها. سوف تُساعد هذه الإجراءات في الحفاظ على البيئة.

 

-                 المادة الفعَّالة هي إيِبيِروبِيسين هيدروكلوريد.

-                 المكونات الأخرى هي كلوريد الصوديوم، حمض الهيدروكلوريك، ماء للحقن.

 

يحتوي كل مللي لتر من المحلول على 2 مجم من إيِبيِروبِيسين هيدروكلوريد.

 

زجاجة 5 مللي لتر: تحتوي كل زجاجة على 10 مجم من إيِبيِروبِيسين هيدروكلوريد.

زجاجة 25 مللي لتر: تحتوي كل زجاجة على 50 مجم من إيِبيِروبِيسين هيدروكلوريد.

زجاجة 50 مللي لتر: تحتوي كل زجاجة على 100 مجم من إيِبيِروبِيسين هيدروكلوريد.

زجاجة 100 مللي لتر: تحتوي كل زجاجة على 200 مجم من إيِبيِروبِيسين هيدروكلوريد.

 

المحلول معد للحَقْن والتَّسريب وهو محلول صاف أحمر اللون.

 

هذا المنتج الدَّوائي هو محلول معد للحَقْن.

عبوة بها زجاجة واحدة أو 5 أو 10 زجاجات بها 5 مللي لتر من المحلول.

عبوة بها زجاجة واحدة أو 5 أو 10 زجاجات بها 25 مللي لتر من المحلول.

عبوة بها زجاجة واحدة أو 5 أو 10 زجاجات بها 50 مللي لتر من المحلول.

عبوة بها زجاجة واحدة أو 5 أو 10 زجاجات بها 100 مللي لتر من المحلول.

 

قد تكون الزجاجات مغلفة بمادة بلاستيكية واقية (ONKO-SAFE). الغلاف البلاستيكي الواقي (ONKO-SAFE) لا يُلامس المنتج الدَّوائي ويُزيد من الأمان أثناء النقل لطاقم الأطباء والصيادلة.

 

قد لا يتم تسويق جميع أحجام العبوات.

مالك حق التسويق

شركة إيبيفيه فارما المحدودة Nfg.KG أ-4866 أونتراخ، النمسا

04/2020
 Read this leaflet carefully before you start using this product as it contains important information for you

Epirubicin “Ebewe” 2 mg/ml solution for injection

Each milliliter (ml) of solution contains 2 mg of epirubicin hydrochloride. 1 vial of 5 ml solution contains 10 mg epirubicin hydrochloride. 1 vial of 25 ml solution contains 50 mg epirubicin hydrochloride. 1 vial of 50 ml solution contains 100 mg epirubicin hydrochloride. 1 vial of 100 ml solution contains 200 mg epirubicin hydrochloride. The medicinal product contains 0.154 mmol/ml (3.54 mg/ml) sodium. 1 vial of 5 ml solution contains 0.77 mmol (17.70 mg) sodium. 1 vial of 25 ml solution contains 3.85 mmol (88.52 mg) sodium. 1 vial of 50 ml solution contains 7.70 mmol (177.02 mg) sodium. 1 vial of 100 ml solution contains 15.40 mmol (354.05 mg) sodium. For the full list of excipients, see section 6.1.

Solution for injection and infusion Product description: clear, red solution

Epirubicin is used in the treatment of a range of neoplastic conditions including;

-     Carcinoma of the breast

-     Gastric cancer

 

When administered intravesically, epirubicin has been shown to be beneficial in the treatment of;

-     Papillary transitional cell carcinoma of the bladder

-     Carcinoma-in-situ of the bladder

-     Intravesical prophylaxis of recurrences of superficial bladder carcinoma following transurethral resection.


Epirubicin "Ebewe" is for intravenous or intravesical use only.

The safety and efficacy of Epirubicin "Ebewe"in children has not been established.

 

Intravenous administration

It is advisable to administer Epirubicin "Ebewe"  via the tubing of a free-running intravenous saline infusion after checking that the needle is properly placed in the vein. Care should be taken to avoid extravasation (see Section 4.4). In case of extravasation, administration should be stopped immediately.

 

Conventional dose

When epirubicin hydrochloride is used as a single agent, the recommended dosage in adults is 60-90 mg/m2 body area. Epirubicin hydrochloride should be injected intravenously over 3-5 minutes. The dose should be repeated at 21-day intervals, depending upon the patient’s haematological status and bone marrow function.

If signs of toxicity, including severe neutropenia/neutropenic fever and thrombocytopenia occur (which could persist at day 21), dose modification or postponement of the subsequent dose may be required.

 

High dose

For high dose treatment, epirubicin hydrochloride may be given as an intravenous bolus over 3-5 minutes or as an infusion of up to 30 minutes duration.

 

1.1        Breast Cancer

In the adjuvant treatment of early breast cancer patients with positive lymph nodes, intravenous doses of epirubicin hydrochloride ranging from 100 mg/m2 (as a single dose on day 1) to 120 mg/m2 (in two divided doses on days 1 and 8) every 3-4 weeks, in combination with intravenous cyclophosphamide and 5- fluorouracil and oral tamoxifen, are recommended.

Lower doses (60-75 mg/m2 for conventional treatment and 105-120 mg/m2 for high dose treatment) are recommended for patients whose bone marrow function has been impaired by previous chemotherapy or radiotherapy, by age, or neoplastic bone marrow infiltration. The total dose per cycle may be divided over 2-3 successive days.

 

 

Doses for intravenous administration:

The following doses of epirubicin hydrochloride are commonly used in monotherapy and combination chemotherapy for various tumours, as shown:

 

Cancer Indication

Epirubicin hydrochloride Dose (mg/m2)a

Monotherapy

Combination Therapy

Gastric cancer

60–90

50

a)Doses generally given Day 1 or Day 1, 2 and 3 at 21-day intervals

 

Combination therapy

If Epirubicin "Ebewe" is used in combination with other cytotoxic products, the dose should be reduced accordingly. Commonly used doses are shown in the table above.

In establishing the maximal cumulative doses of epirubicin hydrochloride (usually: 720 – 1000 mg/m2), any concomitant therapy with potentially cardiotoxic drugs should be taken into account.

 

1.2        Impaired liver function

The major route of elimination of epirubicin hydrochloride is the hepatobiliary system. In patients with impaired liver function the dose should be reduced based on serum bilirubin levels as follows:

Serum Bilirubin            Dose Reduction

24 - 51 μmol/l               50%

> 51 μmol/l                   75%

 

1.3        Impaired renal function

Moderate renal impairment does not appear to require a dose reduction in view of the limited amount of epirubicin hydrochloride excreted by this route. However, dosage adjustment may be necessary in patients with serum creatinine >5 mg/dL.

 

1.4        Intravesical administration

Epirubicin hydrochloride can be given by intravesical administration for the treatment of superficial bladder cancer and carcinoma-in-situ. It should not be given intravesically for the treatment of invasive tumours that have penetrated the bladder wall, systemic therapy or surgery is more appropriate in these situations (see Section 4.3). Epirubicin hydrochloride has also been successfully used intravesically as a prophylactic agent after transurethral resection of superficial tumours to prevent recurrence.

 

Doses for  intravesical administration:

The following doses of epirubicin hydrochloride are commonly used in monotherapy for bladder cancer:

 

 

Monotherapy

Bladder cancer

50 mg/50 ml or 80 mg/50 ml (carcinoma in situ)

Prophylaxis:

50 mg/50 ml weekly for 4 weeks then monthly for 11 months

 

For the treatment of superficial bladder cancer the following regimen is recommended, using the dilution table below:

 

8 weekly instillations of 50 mg/50 ml (diluted with saline or distilled sterile water).

 

If local toxicity is observed: A dose reduction to 30 mg/50 ml is advised.

 

Carcinoma-in-situ of the bladder: Up to 80 mg/50 ml (depending on individual tolerability of the patient)

 

For prophylaxis: 4 weekly administrations of 50 mg/50 ml followed by 11 monthly instillations at the same dose.

 

 

2        DILUTION TABLE FOR BLADDER INSTILLATION SOLUTIONS

 

Dose Epirubicin hydrochloride required

Volume of Epirubicin "Ebewe" 2 mg/ml solution for injection

Volume of diluent sterile water for injection or 0.9% sterile saline

Total volume for bladder installation

30 mg

15 ml

35 ml

50 ml

50 mg

25 ml

25 ml

50 ml

80 mg

40 ml

10 ml

50 ml

 

The solution should be retained intravesically for 1-2 hours. To avoid undue dilution with urine, the patient should be instructed not to drink any fluid in the 12 hours prior to instillation. During the instillation, the patient should be rotated occasionally and should be instructed to void urine at the end of the instillation time.

 


- Hypersensitivity to epirubicin or any other component of the product, other anthracyclines or antracenediones. - Lactation Intravenous use - Persistent myelosuppression myocardiopathy - Previous treatments with maximal cumulative doses of epirubicin hydrochloride and/or other anthracyclines and antracenediones (see section 4.4) - Recent myocardial infarction Severe arrhythmias - Patients with acute systemic infections - Sever hepatic impairment - Unstable angina pectoris - Severe mucositis of the mouth, pharynx, oeasophagus, and gastro-intestinal tract. Intravesical use - Urinary tract infections - Inflammation of the bladder - Hematuria - Invasive tumours penetrating the bladder - Catheterisation problems - Vesical inflammation - Large volume of residual urine - Contracted bladder.

General

Epirubicin should be administered only under the supervision of qualified physicians experienced in the use of cytotoxic therapy.

 

Patients should recover from acute toxicities (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) of prior cytotoxic treatment before beginning treatment with epirubicin.

 

While treatment with high doses of epirubicin hydrochloride (e.g. ≥ 90 mg/m2 every 3 to 4 weeks) causes adverse events generally similar to those seen at standard doses (< 90 mg/m2 every 3 to 4 weeks), the severity of the neutropenia and stomatitis/mucositis may be increased. Treatment with high doses of epirubicin hydrochloride does require special attention for possible clinical complications due to profound myelosuppression.

 

Cardiac function

Cardiotoxicity is a risk of anthracycline treatment that may be manifested by early (i.e. acute) or late (i.e. delayed) events.

 

Early (i.e. acute) events

Early cardiotoxicity of epirubicin consists mainly of sinus tachycardia and/or electrocardiogram (ECG) abnormalities such as non-specific ST-T wave changes. Tachyarrhythmias, including premature ventricular contractions, ventricular tachycardia and bradycardia, as well as atrioventricular and bundle-branch block have also been reported. These effects do not usually predict subsequent development of delayed cardiotoxicity, are rarely of clinical importance, and are generally not a consideration for the discontinuation of epirubicin treatment.

 

Late (i.e. delayed) events

Delayed cardiotoxicity usually develops late in the course of therapy with epirubicin or within 2 to 3 months after treatment termination, but later events (several months to years after completion of treatment) have also been reported. Delayed cardiomyopathy is manifested by reduced left ventricular ejection fraction (LVEF) and/or signs and symptoms of congestive heart failure (CHF) such as dyspnea, pulmonary edema, dependent edema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion and gallop rhythm. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy and represents the cumulative dose-limiting toxicity of the drug.

 

The risk of developing CHF increases rapidly with increasing total cumulative doses of epirubicin hydrochloride in excess of 900 mg/m2; this cumulative dose should only be exceeded with extreme caution. (see section 5.1)

 

Cardiac function should be assessed before patients undergo treatment with epirubicin and must be monitored throughout therapy to minimize the risk of incurring severe cardiac impairment. The risk may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of epirubicin at the first sign of impaired function. The appropriate quantitative method for repeated assessment of cardiac function (evaluation of LVEF) includes multi-gated radionuclide angiography (MUGA) or echocardiography (ECHO). A baseline cardiac evaluation with an ECG and either a MUGA scan or an ECHO is recommended, especially in patients with risk factors for increased cardiotoxicity. Repeated MUGA or ECHO determinations of LVEF should be performed, particularly with higher, cumulative anthracycline doses. The technique used for assessment should be consistent throughout follow-up.

 

Given the risk of cardiomyopathy, a cumulative dose of 900 mg/m2 epirubicin hydrochloride should be exceeded only with extreme caution.

 

Risk factors for cardiac toxicity include active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, concomitant use of other drugs with the ability to suppress cardiac contractility or cardiotoxic drugs (e.g. trastuzumab) (see section 4.5 Interaction with other medicinal products and other forms of interaction) with an increased risk in the elderly.

 

Heart failure (New York Heart Association [NYHA] class II-IV) has been observed in patients receiving trastuzamab therapy alone or in combination with anthracyclines such as epirubicin. This may be moderate to severe and has been associated with death.

Trastuzumab and anthracyclines such as epirubicin should not be used currently in combination except in a well-controlled clinical trial setting with cardiac monitoring. Patients who have previously received anthracyclines are also at risk of cardiotoxicity with trastuzumab treatment, although the risk is lower than with concurrent use of traztuzumab and anthracyclines.

 

Because the half-life of trastuzumab is approximately 28-38 days, trastuzumab may persist in the circulation for up to 27 weeks after stopping trastuzumab treatment. Patients who receive anthracyclines such as epirubicin after stopping trastuzumab may possibly be at increased risk of cardiotoxicity. If possible, physicians should avoid anthracycline-based therapy for up to 27 weeks after stopping trastuzumab. If anthracyclines such as epirubicin are used, the patient’s cardiac function should be monitored carefully.

 

If symptomatic cardiac failure develops during trastuzumab therapy after epirubicin therapy, it should be treated with the standard medications for this purpose

 

Cardiac function monitoring must be particularly strict in patients receiving high cumulative doses and in those with risk factors. However, cardiotoxicity with epirubicin may occur at lower cumulative doses whether or not cardiac risk factors are present.

It is probable that the toxicity of epirubicin and other anthracyclines or anthracenediones is additive.

 

Hematologic toxicity

As with other cytotoxic agents, epirubicin may produce myelosuppression. Hematologic profiles should be assessed before and during each cycle of therapy with epirubicin, including differential white blood cell (WBC) counts. A dose-dependent, reversible leukopenia and/or granulocytopenia (neutropenia) is the predominant manifestation of epirubicin hematologic toxicity and is the most common acute dose-limiting toxicity of this drug. Leukopenia and neutropenia are generally more severe with high-dose schedules, reaching the nadir in most cases between days 10 and 14 after drug administration; this is usually transient with the WBC/neutrophil counts returning to normal values in most cases by day 21. Thrombocytopenia and anemia may also occur. Clinical consequences of severe myelosuppression include fever, infection, sepsis/septicemia, septic shock, hemorrhage, tissue hypoxia or death.

 

Secondary leukemia

Secondary leukemia, with or without a preleukemic phase, has been reported in patients treated with anthracyclines, including epirubicin. Secondary leukemia is more common when such drugs are given in combination with DNA-damaging antineoplastic agents, in combination with radiation treatment, when patients have been heavily pre-treated with cytotoxic drugs, or when doses of the anthracyclines have been escalated. These leukemias can have a 1- to 3-year latency period.

 

Gastrointestinal

Epirubicin is emetigenic. Mucositis/stomatitis generally appears early after drug administration and, if severe, may progress over a few days to mucosal ulcerations. Most patients recover from this adverse event by the third week of therapy.

 

Liver function

The major route of elimination of epirubicin is the hepatobiliary system. Serum total bilirubin and AST levels should be evaluated before and during treatment with epirubicin. Patients with elevated bilirubin or AST may experience slower clearance of drug with an increase in overall toxicity. Lower doses are recommended in these patients (see section 4.2 Posology and administration). Patients with severe hepatic impairment should not receive epirubicin (see section 4.3 Contraindications).

 

Renal function

Serum creatinine should be assessed before and during therapy. Dosage adjustment is necessary in patients with serum creatinine > 5 mg/dL (see section 4.2 Posology and method of administration).

 

Effects at site of injection

Phlebosclerosis may result from an injection into a small vessel or from repeated injections into the same vein. Following the recommended administration procedures may minimize the risk of phlebitis/thrombophlebitis at the injection site (see section 4.2 Posology and method of administration).

 

Extravasation

Extravasation of epirubicin during intravenous injection may produce local pain, severe tissue lesions (vesication, severe cellulitis) and necrosis. Should signs or symptoms of extravasation occur during intravenous administration of epirubicin, the drug infusion should be immediately discontinued. The adverse effect of extravasation of anthracyclines may be prevented or reduced by immediate use of a specific treatment e.g. dexrazoxane (please refer to relevant labels for use).The patient’s pain may be relieved by cooling down the area and keeping it cool, use of hyaluronic acid and DMSO. The patient should be monitored closely during the subsequent period of time, as necrosis may occur after several weeks. If extravasation occurs, a plastic surgeon should be consulted with a view to possible excision.

 

Other

As with other cytotoxic agents, thrombophlebitis and thromboembolic phenomena, including pulmonary embolism (in some cases fatal), have been coincidentally reported with the use of epirubicin.

 

Tumor-lysis syndrome

Epirubicin may induce hyperuricemia because of the extensive purine catabolism that accompanies rapid drug-induced lysis of neoplastic cells (tumor-lysis syndrome). Blood uric acid levels, potassium, calcium phosphate and creatinine should be evaluated after initial treatment. Hydration, urine alkalinization and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor-lysis syndrome.

 

Immunosuppressant effects/Increased susceptibility to infections

Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including epirubicin, may result in serious or fatal infections (see section 4.5 Interaction with other medicinal products and other forms of interactions). Vaccination with a live vaccine should be avoided in patients receiving epirubicin. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.

 

Reproductive systemEpirubicin can cause genotoxicity. Men and women treated with epirubicin should adopt appropriate contraceptives. Patients desiring to have children after completion of therapy should be advised to obtain genetic counselling if appropriate and available.

 

Additional warnings and precautions for other routes of administration

 

Intravesical route

Administration of epirubicin may produce symptoms of chemical cystitis (such as dysuria, polyuria, nocturia, stranguria, hematuria, bladder discomfort, necrosis of the bladder wall) and bladder constriction. Special attention is required for catheterization problems (e.g. uretheral obstruction due to massive intravesical tumors).

 

Intra-arterial route

Intra-arterial administration of epirubicin (transcatheter arterial embolization for the localized or regional therapies of primary hepatocellular carcinoma or liver metastases) may produce (in addition to systemic toxicity qualitatively similar to that observed following intravenous administration of epirubicin) localized or regional events which include gastro-duodenal ulcers (probably due to reflux of the drugs into the gastric artery) and narrowing of bile ducts due to drug-induced sclerosing cholangitis. This route of administration can lead to widespread necrosis of the perfused tissue.


Epirubicin is mainly used in combination with other cytotoxic drugs. Additive toxicity may occur especially with regard to bone marrow/hematologic and gastro-intestinal effects (see section 4.4 Special warnings and precautions for use).

The use of epirubicin in combination chemotherapy with other potentially cardiotoxic drugs, as well as the concomitant use of other cardioactive compounds (e.g. calcium channel blockers), requires monitoring of cardiac function throughout treatment.

 

Epirubicin is extensively metabolized by the liver. Changes in hepatic function induced by concomitant therapies may affect epirubicin metabolism, pharmacokinetics, therapeutic efficacy and/or toxicity (see section 4.4 Special warnings and precautions for use).

 

Anthracyclines including epirubicin should not be administered in combination with other cardiotoxic agents unless the patient’s cardiac function is closely monitored. Patients receiving anthracyclines after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity.

Because the half-life of trastuzumab is approximately 28-38 days, trastuzumab may persist in the circulation for up to 27 weeks after stopping trastuzumab treatment. Patients who receive anthracyclines such as epirubicin hydrochloride after stopping trastuzumab may possibly be at an increased risk of cardio toxicity. If possible, physicians should avoid anthracycline-based therapy for up to 27 weeks after stopping trastuzumab. If anthracyclines such as epirubicin hydrochloride are used, the patient’s cardiac function should be monitored carefully.

 

Vaccination with a live vaccine should be avoided in patients receiving epirubicin. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.

 

Cimetidine increased the AUC of epirubicin by 50% and should be discontinued during treatment with epirubicin.

 

When given prior to epirubicin, paclitaxel can cause increased plasma concentrations of unchanged epirubicin and its metabolites, the latter being, however, neither toxic nor active. Coadministration of paclitaxel or docetaxel did not affect the pharmacokinetics of epirubicin when epirubicin was administered prior to the taxane.

This combination may be used if using staggered administration between the two agents. Infusion of epirubicin and paclitaxel should be performed with at least a 24 hour interval between the 2 agents.

 

Dexverapamil may alter the pharmacokinetics of epirubicin and possibly increase its bone marrow depressant effects.

 

One study found that docetaxel may increase the plasma concentrations of epirubicin metabolites when administered immediately after epirubicin.

 

Quinine may accelerate the initial distribution of epirubicin from blood into the tissues and may have an influence on the red blood cells partitioning of epirubicin.

 

The co-administration of interferon α2b may cause a reduction in both the terminal elimination half-life and the total clearance of epirubicin.

 

The possibility of a marked disturbance of haematopoiesis needs to be kept in mind with a (pre) treatment with medications which influences the bone marrow (i.e. cytostatic agents, sulphonamide, chloramphenicol, diphenylhydantoin, amidopyrine-derivate, antiretroviral agents).

 

Increase of myelosuppression may occur in patients receiving combination therapy of anthracycline and dexrazoxane.


Impairment of Fertility

Epirubicin could induce chromosomal damage in human spermatozoa. Men undergoing treatment with epirubicin should use effective contraceptive methods and if appropriate and available, seek advice on sperm preservation due to the possibility of irreversible infertility caused by therapy.

Epirubicin may cause amenorrhea or premature menopause in premenopausal women.

 

Pregnancy

Women of child-bearing potential should be advised to avoid becoming pregnant during treatment and should use effective contraceptive methods. Male patients treated with epirubicin are advised not to father a child during and up to 6 months after treatment.

 

Experimental data in animals suggest that epirubicin may cause foetal harm when administered to a pregnant woman. If epirubicin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the foetus.

 

There are no studies in pregnant women. Epirubicin should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

 

Breastfeeding

It is not known whether epirubicin is excreted in human milk. Because many drugs, including other anthracyclines, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from epirubicin, mothers should discontinue nursing prior to taking this drug.


There have been no reports of particular adverse events relating to the effects on ability to drive and to use machines.

 

Epirubicin may cause episodes of nausea and vomiting, which can temporarily lead to an impairment of ability to drive or operate machines.


The following undesirable effects have been observed and reported during treatment with epirubicin with the following frequencies: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated form the available data)

 

More than 10% of treated patients can expect to develop undesirable effects. The most common undesirable effects are myelosuppression, gastrointestinal side effects, anorexia, alopecia, infection.

 

System organ class

Frequency

Undesirable effects

Infections and infestations

Common

Infection

Not known

Septic shock, sepsis, pneumonia

Neoplasms benign, malignant and unspecified (incl. cysts and polyps)

Rare

Acute lymphocytic leukaemia, acute myelogenous leukaemia

Blood and the lymphatic system disorders

Very common

Myelosuppression (leukopenia, granulocytopenia and neutropenia, anaemia and febrile neutropenia)

Uncommon

Thrombocytopenia

Not known

Haemorrhage and tissue hypoxia as result of myelosuppression

Immune system disorders

Rare

Anaphylaxis

Metabolism and nutrition disorders

Common

Anorexia, dehydration

Rare

Hyperuricemia (see section 4.4)

Nervous system disorders

Rare

Dizziness

Eye disorders

Not known

Conjunctivitis, keratitis

Cardiac disorders

Rare

Congestive heart failure, (dyspnoea; oedema, hepatomegaly, ascites, pulmonary oedema, pleural effusions, gallop rhythm) cardiotoxicity (e.g. ECG abnormalities, arrhythmias, cardiomyopathy), ventricular tachycardia, bradycardia, AV block, bundle-branch block

Vascular disorders

Common

Hot flashes

Uncommon

Phlebitis, thrombophlebitis

Not known

Shock, thromboembolism, including pulmonary emboli

Gastrointestinal disorders

Common

Mucositis, esophagitis, stomatitis, vomiting, diarrhoea, nausea

 

Not known

Oral mucosa erosion, mouth ulceration, oral pain, mucosal burning sensation, mouth haemorrhage, and buccal pigmentation

Skin and subcutaneous tissue disorders

Very common

Alopecia

Rare

Urticaria

Not known

Local toxicity, rash, itch, skin changes, erythema, flushes, skin and nail hyperpigmentation, photosensitivity, hypersensitivity to irradiated skin (radiation-recall reaction)

Renal and urinary disorders

Very common

Red coloration of urine for 1 to 2 days after administration

Reproductive system and breast disorders

Rare

Amenorrhea, azoospermia

General disorders and administration site conditions

Common

Infusion site erythema

Rare

Malaise, asthenia, fever, chills

 

Not known

Phlebosklerosis, local pain, severe cellulitis, tissue necrosis after accidental paravenous injection

Investigations

Rare

Changes in transaminase levels

Not Known

Asymptomatic drops in left ventricular ejection fraction

Injury, poisoning and procedural complications

Common

Chemical cystitis, sometimes haemorrhagic, has been observed following intravesical administration (see section 4.4)

 

Intravesical administration

As only a small amount of active ingredient is reabsorbed after intravesical instillation, severe systemic adverse drug reactions as well as allergic reactions are rare. Commonly reported are local reactions like burning sensation and frequent voiding (pollakisuria).Occasional bacterial or chemical cystitis have been reported (see section 4.4 Special warnings and precautions for use). These ADRs are mostly reversible.

 


Acute overdosage with epirubicin will result in severe myelosuppression (mainly leukopenia and thrombocytopenia), gastrointestinal toxic effects (mainly mucositis) and acute cardiac complications. Latent cardiac failure has been observed with anthracyclines several months to years after completion of treatment (see section 4.4 Special warnings and precautions for use). Patients must be carefully monitored. If signs of cardiac failure occur, patients should be treated according to conventional guidelines.

 

Treatment

Symptomatic; Epirubicin cannot be removed by dialysis.


Pharmacotherapeutic group: Antineoplastic agent. ATC code: L01D B03


Epirubicin is a cytotoxic active antibiotic from the anthracycline group.
The mechanism of action of epirubicin is related to its ability to bind to DNA. Cell culture studies have shown rapid cell penetration, localisation in the nucleus and inhibition of nucleic acid synthesis and mitosis. Epirubicin has proved to be active on a wide spectrum of experimental tumours including L1210 and P388 leukaemias, sarcomas SA180 (solid and ascitic forms), B16 melanoma, mammary carcinoma, Lewis lung carcinoma and colon carcinoma 38. It has also shown activity against human tumours transplanted into athymic nude mice (melanoma, mammary, lung, prostatic and ovarian carcinomas).


In patients with normal hepatic and renal function, plasma levels after intravenous injection of 60-150 mg/m2 of the drug follow a tri-exponential decreasing pattern with a very fast first phase and a slow terminal phase with a mean half-life of about 40 hours. These doses are within the limits of pharmacokinetic linearity both in terms of plasma clearance values and metabolic pathway. Between 60 and 120 mg/m2 there is an extensive linear pharmacokinetic, 150 mg/m2 is at the margin of dose linearity. The major metabolites that have been identified are epirubicinol (13-OH epirubicin) and glucuronides of epirubicin and epirubicinol.

 

In pharmacokinetic studies of patients with carcinoma in situ of the bladder the plasma levels of epirubicin after intravesical instillation are typically low (<10 ng/ml). a significant systemic resorption can therefore not be assumed. In patients with lesions of the mucosa of the bladder (e.g. tumour, cystitis, operations), a higher resorption rate can be expected.

The 4’-O-glucuronidation distinguishes epirubicin from doxorubicin and may account for the faster elimination of epirubicin and its reduced toxicity. Plasma levels of the main metabolite, the 13-OH derivative (epirubicinol) are consistently lower and virtually parallel those of the unchanged drug.

 

Epirubicin is eliminated mainly through the liver; high plasma clearance values (0.9 l/min) indicate that this slow elimination is due to extensive tissue distribution. Urinary excretion accounts for approximately 9-10% of the administered dose in 48 hours.

 

Biliary excretion represents the major route of elimination, about 40% of the administered dose being recovered in the bile in 72 hours. The drug does not cross the blood brain barrier.

 


Following repeated dosing with epirubicin, the target organs in rat, rabbit and dog were the haemolymphopoietic system, GI tract, kidney, liver and reproductive organs. Epirubicin was also cardiotoxic in the rat, rabbit and dog.

 

Epirubicin, like other anthracyclines, was mutagenic, genotoxic, embryotoxic and carcinogenic in rats.

 

No malformations were seen in rats or rabbits, but like other anthracyclines and cytotoxic drugs, epirubicin must be considered potentially teratogenic.

 

A local tolerance study in rats and mice showed extravasation of epirubicin causes tissue necrosis.

 


Sodium chloride,

hydrochloric acid (for ph adjustment),

water for injections.

 


Prolonged contact of the medicinal product with any solution of an alkaline pH should be avoided: this will result in hydrolysis (degradation) of the active substance.  A physical incompatibility of the product with heparin has been reported.  This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

 


Medicinal product as packaged for sale: 2 years Shelf life after dilution: Chemical and physical in-use stability has been demonstrated for 7 days at 2 to 8°C in Glucose 5 % or Sodium Chloride 0.9 %. In use: From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8ºC.

Store refrigerated (2°C to 8ºC). For storage conditions after dilution of the medicinal product, see section 6.3.

 

Storage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15° to 25°C).

 


Type 1  glass vials with a rubber (chlorobutyl) stopper with/without a protective plastic overwrap (ONKO-SAFE).

 

Packs of

1 vial, 5 or 10 vials containing 5 ml of solution.

1 vial, 5 or 10 vials containing 25 ml of solution.

1 vial, 5 or 10 vials containing 50 ml of solution.

1 vial, 5 or 10 vials containing 100 ml of solution.

 

Not all pack sizes may be marketed.


Epirubicin Hydrochloride 2 mg/ml Injection may be further diluted in Glucose 5% or Sodium Chloride 0.9% and administered as an intravenous infusion. The infusion solution should be prepared immediately before use.

For instructions on the administration of the product, see section 4.2.

The injection solution contains no preservative and any unused portion of the vial should be discarded immediately.

 

Guidelines for the safe handling and disposal of antineoplastic agents:

 

  1. If an infusion solution is to be prepared, this should be performed by trained personnel under aseptic conditions.
     
  2. Preparation of an infusion solution should be performed in a designated aseptic area.
     
  3. Adequate protective disposable gloves, goggles, gown and mask should be worn.
     
  4. Precautions should be taken to avoid the medicinal product accidentally coming into contact with the eyes. In the event of contact with the eyes, irrigate with large amounts of water and/or 0.9% sodium chloride solution. Then seek medical evaluation by a physician.
     
  5. In case of skin contact, thoroughly wash the affected area with soap and water or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Always wash hands after removing gloves.
     
  6. Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All cleaning materials should be disposed of as detailed below.
     
  7. Pregnant staff should not handle the cytotoxic preparation.
     
  8. Adequate care and precautions should be taken in the disposal of items (syringes, needles etc) used to reconstitute and/or dilute cytotoxic medicinal products. Any unused product or waste material should be disposed of in accordance with local requirements.

 


EBEWE Pharma Ges.m.b.H. Nfg.KG A-4866 Unterach, AUSTRIA

04/2020
}

صورة المنتج على الرف

الصورة الاساسية