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Eranza contains ertapenem which is an antibiotic of the beta-lactam group. It has the ability to kill a wide range of bacteria (germs) that cause infections in various parts of the body.
Eranza can be given to persons 3 months of age and older.
Treatment:
Your doctor has prescribed Eranza because you or your child has one (or more) of the following types of infection:
- Infection in the abdomen
- Infection affecting the lungs (pneumonia)
- Gynaecological infections
- Skin infections of the foot in diabetic patients.
Prevention:
- Prevention of surgical site infections in adults following surgery of the colon or rectum
Do not have Eranza
- If you are allergic to the active substance (ertapenem) or any of the other ingredients of this medicine (listed in section 6)
- If you are allergic to antibiotics such as penicillins, cephalosporins or carbapenems (which are used to treat various infections).
Warnings and Precautions
Talk to your doctor, nurse or pharmacist before taking Eranza.
During treatment, if you experience an allergic reaction (such as swelling of the face, tongue or throat, difficulty in breathing or swallowing, skin rash), tell your doctor straight away as you may need urgent medical treatment.
While antibiotics including Eranza kill certain bacteria, other bacteria and fungi may continue to grow more than normal. This is called overgrowth. Your doctor will monitor you for overgrowth and treat you if necessary.
It is important that you tell your doctor if you have diarrhoea before, during or after your treatment with Eranza. This is because you may have a condition known as colitis (an inflammation of the bowel). Do not take any medicine to treat diarrhoea without first checking with your doctor.
Tell your doctor if you are taking medicines called valproic acid or sodium valproate (see Other medicines and Eranza below).
Tell your doctor about any medical condition you have or have had including:
- Kidney disease. It is particularly important that your doctor knows if you have kidney disease and whether you undergo dialysis treatment.
- Allergies to any medicines, including antibiotics
- Central nervous system disorders, such as localized tremors, or seizures.
Children and adolescents (3 months to 17 years of age)
Experience with ertapenem is limited in children less than two years of age. In this age group your doctor will decide on the potential benefit of its use. There is no experience in children under 3 months of age.
Other medicines and Eranza
Always tell your doctor about all medicines that you are taking or plan to take, including those obtained without a prescription.
Tell your doctor, nurse or pharmacist if you are taking medicines called valproic acid or sodium valproate (used to treat epilepsy, bipolar disorder, migraines, or schizophrenia). This is because Eranza can affect the way some other medicines work. Your doctor will decide whether you should use Eranza in combination with these other medicines.
Pregnancy and breast-feeding
It is important that you tell your doctor if you are pregnant or are planning to become pregnant before receiving Eranza.
Ertapenem has not been studied in pregnant women. Eranza should not be used during pregnancy unless your doctor decides the potential benefit justifies the potential risk to the foetus.
It is important that you tell your doctor if you are breast-feeding or if you intend to breast-feed before receiving Eranza.
Women who are receiving ertapenem should not breast-feed, because it has been found in human milk and the breast-fed baby may therefore be affected.
Driving and using machines
Do not drive or use any tools or machines until you know how you react to the medicine.
Certain side effects, such as dizziness and sleepiness, have been reported with ertapenem, which may affect some patients’ ability to drive or operate machinery.
Eranza contains sodium
Eranza contains sodium. Eranza contains approximately 6.0 mEq (approximately 137 mg) of sodium per 1000 mg dose which should be taken into consideration by patients on a controlled sodium diet
Eranza will always be prepared and given to you intravenously (into a vein) by a doctor or another healthcare professional.
The recommended dose of Eranza for adults and adolescents 13 years of age and older is 1000 mg given once a day. The recommended dose for children 3 months to 12 years of age is 15 mg/kg given twice daily (not to exceed 1000 mg/day). Your doctor will decide how many days treatment you need.
For prevention of surgical site infections following surgery of the colon or rectum, the recommended dose of Eranza is 1000 mg administered as a single intravenous dose 1 hour before surgery.
It is very important that you continue to receive Eranza for as long as your doctor prescribes it.
If you are given more Eranza than you should
If you are concerned that you may have been given too much Eranza, contact your doctor or another healthcare professional immediately.
If you miss a dose of Eranza
If you are concerned that you may have missed a dose, contact your doctor or another healthcare professional immediately.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Adults 18 years of age and older:
Since ertapenem has been marketed, severe allergic reactions (anaphylaxis), hypersensitivity syndromes (allergic reactions including rash, fever, abnormal blood tests) have been reported. The first signs of a severe allergic reaction may include swelling of the face and/or throat. If these symptoms occur tell your doctor straight away as you may need urgent medical treatment.
The most common (more than 1 in 100 patients and less than 1 in 10 patients) side effects are:
- Headache
- Diarrhoea, nausea, vomiting
- Rash, itching
- Problems with the vein into which the medicine is given (including inflammation, formation of a lump, swelling at the injection site, or leaking of fluid into the tissue and skin around the injection site)
- Increase in platelet count
- Changes in liver function tests
Less common (more than 1 in 1,000 patients and less than 1 in 100 patients) side effects are:
- Dizziness, sleepiness, sleeplessness, confusion, seizure
- Low blood pressure, slow heart rate
- Shortness of breath, sore throat
- Constipation, yeast infection of the mouth, antibiotic associated diarrhoea, acid regurgitation, dry mouth, indigestion, loss of appetite
- Skin redness
- Vaginal discharge and irritation
- Abdominal pain, fatigue, fungal infection, fever, oedema/swelling, chest pain, abnormal taste
- Changes in some laboratory blood and urine tests
Side effects reported rarely (more than 1 in 10,000 patients and less than 1 in 1,000 patients) are:
- Decrease in white blood cells, decrease in blood platelet count
- Low blood sugar
- Agitation, anxiety, depression, tremor
- Irregular heart rate, increased blood pressure, bleeding, fast heart rate
- Nasal congestion, cough, bleeding from the nose, pneumonia, abnormal breathing sounds, wheezing
- Inflammation of the gall bladder, difficulty in swallowing, faecal incontinence, jaundice, liver disorder
- Inflammation of the skin, fungal infection of the skin, skin peeling, infection of the wound after an operation
- Muscle cramp, shoulder pain
- Urinary tract infection, kidney impairment
- Miscarriage, genital bleeding
- Allergy, feeling unwell, pelvic peritonitis, changes to the white part of the eye, fainting.
Side effects reported (frequency not known) since ertapenem has been marketed are:
- Hallucinations
- Decreased consciousness
- Altered mental status (including aggression, delirium, disorientation, mental status changes)
- Abnormal movements
- Muscle weakness
- Unsteady walking
- Teeth staining
There have also been reports of changes in some laboratory blood tests.
Children and adolescents (3 months to 17 years of age):
The most common (more than 1 in 100 patients and less than 1 in 10 patients) side effects are:
- Diarrhoea
- Diaper rash
- Pain at the infusion site
- Changes in white blood cell count
- Changes in liver function tests
Less common (more than 1 in 1,000 patients and less than 1 in 100 patients) side effects are:
- Headache
- Hot flush, high blood pressure, red or purple, flat, pinhead spots under the skin
- Discoloured faeces, black tar-like faeces
- Skin redness, skin rash
- Burning, itching, redness and warmth at infusion site, redness at injection site
- Increase in platelet count
- Changes in some laboratory blood tests
Side effects reported (frequency not known) since ertapenem has been marketed are:
- Hallucinations
- Altered mental status (including aggression
Keep this medicine out of the sight and reach of children.
Do not store above 25°C.
Store in the original package.
Do not use this medicine after the expiry date which is stated on the package after “EXP”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any visible signs of deterioration.
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 ertapenem sodium. Each vial contains 1046 mg ertapenem sodium equivalent to 1000 mg ertapenem.
The other ingredients are sodium hydrogen carbonate and sodium hydroxide.
Marketing Authorization Holder
Jazeera Pharmaceutical Industries
Al-Kharj Road
P.O. BOX 106229
Riyadh 11666, Saudi Arabia
Tel: + (966-11) 8107023, + (966-11) 2142472
Fax: + (966-11) 2078170
e-mail: jpimedical@hikma.com
Manufacturer
ACS Dobfar S.p.A.
Nucleo Industriale S.Atto
64100 Teramo
Italy
For any information about this medicine, please contact the local representative of the Marketing Authorization Holder:
• Saudi Arabia
Tel: + (966-11) 4173731 Ext: 1086
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 (see details below). By reporting side effects, you can also help provide more information on the safety of this medicine.
· Saudi Arabia
The National Pharmacovigilance Center (NPC)
Fax: + (966-11) 2057662
Call NPC at: + (966-11) 2038222, Exts: 2317-2356-2340.
SFDA Call Center: 19999
e-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa/
· Other GCC States
Please contact the relevant competent authority
يحتوي إيرانزا على إيرتابينام وهو مضاد حيوي من مجموعة بيتا-لاكتام. لديه القدرة على قتل مجموعة كبيرة من البكتيريا (الجراثيم) التي تسبب العدوى في أجزاء مختلفة بالجسم.
يمكن إعطاء إيرانزا للأشخاص من عمر 3 أشهر وما فوق.
العلاج:
لقد وصف لك طبيبك إيرانزا لأنك تعاني أنت أو طفلك من نوع واحد (أو أكثر) من أنواع العدوى التالية:
- عدوى في البطن
- عدوى تؤثر على الرئتين (الالتهاب الرئوي)
- عدوى مرتبطة بأمراض النساء
- عدوى جلدية في القدم لدى مرضى السكري.
الوقاية:
- الوقاية من العدوى عند موضع الجراحة لدى البالغين عقب إجراء جراحة بالقولون أو المستقيم
موانع استخدام إيرانزا
- إذا كنت تعاني من حساسية للمادة الفعّالة (إيرتابينام) أو لأي من المواد الأخرى المستخدمة في تركيبة هذا الدواء (المدرجة في القسم 6)
- إذا كنت تعاني من حساسية للمضادات الحيوية مثل البنسلينات، السيفالوسبورينات أو مضادات كاربابينام الحيوية (التي تستخدم لعلاج العدوى المختلفة).
الاحتياطات والتحذيرات
تحدث مع طبيبك، الممرض أو الصيدلي قبل استخدام إيرانزا.
إذا عانيت أثناء العلاج من رد فعل تحسسي (مثل تورم الوجه، اللسان أو الحلق، صعوبة في التنفس أو البلع، حكة في الجلد)، أخبر طبيبك على الفور حيث قد تحتاج إلى رعاية طبية عاجلة.
قد يستمر نمو فطريات وبكتيريا أخرى بشكل أكثر من المعتاد أثناء عمل المضادات الحيوية، بما فيها إيرانزا، على قتل بعض أنواع البكتيريا. يطلق على ذلك فرط النمو. سيتابع طبيبك حالتك لمعرفة ما إذا كنت تعاني من فرط النمو ويعالجك إذا لزم الأمر.
من المهم أن تخبر طبيبك إذا كنت تعاني من الإسهال قبل، أثناء أو بعد علاجك باستخدام إيرانزا. لأن ذلك يعني احتمالية إصابتك بحالة تعرف باسم التهاب القولون (التهاب في الأمعاء). لا تتناول أي دواء لعلاج الإسهال دون الرجوع إلى طبيبك أولاً.
أخبر طبيبك إذا كنت تتناول أدوية تعرف باسم حمض الفالبرويك أو فالبروات الصوديوم (انظر الأدوية الأخرى وإيرانزا أدناه).
أخبر طبيبك بأي حالة طبية تعاني منها أو عانيت منها بما في ذلك:
- مرض بالكلى. من المهم للغاية أن تبلغ طبيبك ما إذا كنت تعاني من مرض بالكلى وما إذا كنت تخضع للعلاج بالغسيل الكلوي.
- حساسية لأي أدوية، بما في ذلك المضادات الحيوية
- اضطرابات في الجهاز العصبي المركزي، مثل الرعاش الموضعي، أو حدوث النوبات.
الأطفال والمراهقين (من 3 أشهر إلى 17 عاماً)
تجربة إيرتابينام مع الأطفال الذين تقل أعمارهم عن عامين محدودة. سيقرر طبيبك في هذه الفئة العمرية الفائدة المحتملة من استخدامه. لا يوجد خبرة باستخدامه لدى الأطفال الذين تقل أعمارهم عن 3 أشهر.
الأدوية الأخرى وإيرانزا
أخبر طبيبك دائماً بجميع الأدوية التي تتناولها أو تخطط لتناولها، بما في ذلك الأدوية التي يتم الحصول عليها دون وصفة طبية.
أخبر طبيبك، الممرض أو الصيدلي إذا كنت تتناول أدوية يطلق عليها حمض الفالبرويك أو فالبروات الصوديوم (تستخدم لعلاج الصرع، اضطراب ثنائي القطب، الصداع النصفي، أو الانفصام في الشخصية). ذلك لأن إيرانزا قد يؤثر على طريقة عمل بعض الأدوية الأخرى. سيقرر طبيبك ما إذا كان يجب عليك استخدام إيرانزا مع هذه الأدوية الأخرى.
الحمل والرضاعة
من المهم أن تقومي بإبلاغ طبيبك إذا كنتِ حاملاً أو تخططين للحمل قبل أن يتم إعطاؤك إيرانزا.
لم يخضع إيرتابينام للدراسة في النساء الحوامل. ينبغي عدم استخدام إيرانزا أثناء الحمل ما لم يقرر طبيبك أن الفائدة المحتملة تبرر تعريض الجنين للخطر المحتمل.
من المهم أن تخبري طبيبكِ إذا كنتِ تقومين بالرضاعة الطبيعية أو تنوين ذلك قبل أن يتم إعطاؤك إيرانزا.
يجب أن تمتنع النساء اللاواتي يتم إعطاؤهن إيرتابينام عن القيام بالرضاعة الطبيعية، حيث تم إيجاد إيرتابينام في حليب الثدي وذلك قد يؤثر على الطفل الذي يتم إرضاعه.
تأثير إيرانزا على القيادة واستخدام الآلات
تجنب القيادة أو استخدام أي أدوات أو آلات حتى تعرف ردة فعلك تجاه الدواء.
تم الإبلاغ عن بعض الآثار الجانبية المحددة المرتبطة باستخدام إيرتابينام، مثل الدوخة والنعاس، والتي قد تؤثر على قدرة بعض المرضى على القيادة أو تشغيل الآلات.
يحتوي إيرانزا على الصوديوم
يحتوي إيرانزا على الصوديوم. يحتوي إيرانزا تقريباً على 6 مللي مكافئ (حوالي 137 ملغم) من الصوديوم لكل جرعة من 1000 ملغم، ويجب على المرضى الذين يتبعون نظاماً غذائياً منخفض الصوديوم أخذ ذلك في الاعتبار
جب تحضير إيرانزا وإعطاؤك إياه دائماً عن طريق الوريد (في الوريد) من خلال طبيب أو متخصص رعاية صحية آخر.
الجرعة الموصى بها من إيرانزا للبالغين والمراهقين ممن تبلغ أعمارهم 13 عاماً فأكثر هي 1000 ملغم يتم إعطاؤها مرة واحدة يومياً. الجرعة الموصى بها للأطفال بعمر 3 أشهر حتى 12 عاماً هي 15 ملغم/كلغم يتم إعطاؤها مرتين يومياً (مع عدم تجاوز 1000 ملغم/يومياً). سيقرر طبيبك عدد أيام العلاج التي تحتاجها.
الجرعة الموصى بها من إيرانزا هي 1000 ملغم، يتم إعطاؤها كجرعة واحدة عن طريق الوريد قبل العملية الجراحية بساعة واحدة للوقاية من العدوى عند موضع الجراحة عقب إجراء عملية جراحية في القولون أو المستقيم.
من المهم الاستمرار في استعمال إيرانزا طوال المدة التي وصفها لك طبيبك.
إذا تم إعطاؤك جرعة زائدة من إيرانزا
إذا ساورك القلق بأنه قد تم إعطاؤك جرعة زائدة من إيرانزا، اتصل على الفور بطبيبك أو بمتخصص رعاية صحية آخر.
إذا فاتتك جرعة من إيرانزا
إذا ساورك القلق أنه قد فاتتك جرعة، اتصل على الفور بطبيبك أو بمتخصص رعاية صحية آخر.
مثل جميع الأدوية، قد يسبب هذا الدواء آثاراً جانبيةً، إلا أنه ليس بالضرورة أن تحدث لدى جميع مستخدمي هذا الدواء.
البالغين الذين تبلغ أعمارهم 18 عاماً فأكبر:
منذ أن تمّ تسويق إيرتابينام، تم الإبلاغ عن ردود فعل تحسسية شديدة (مثل التأقي)، متلازمات فرط الحساسية (ردود فعل تحسسية تشمل الطفح الجلدي، الحمّى، نتائج فحوصات دم غير طبيعية). قد تشمل العلامات الأولى لرد الفعل التحسسي الشديد تورم الوجه و/أو الحلق. إذا حدثت هذه الأعراض، أخبر طبيبك على الفور لأنك قد تحتاج إلى معالجة طبية عاجلة.
الآثار الجانبية الأكثر شيوعاً (أكثر من 1 من 100 مريض وأقل من 1 من 10 مرضى) هي:
- صداع
- إسهال، غثيان، قيء
- طفح جلدي، حكة
- مشاكل في الوريد الذي يتم إعطاء الدواء من خلاله (بما في ذلك الالتهاب، تشكل كتلة، تورم عند موضع الحقن، أو تسرب السائل إلى الأنسجة والجلد حول موضع الحقن)
- زيادة عدد الصفائح الدموية
- تغيرات في فحوصات وظائف الكبد
الآثار الجانبية الأقل شيوعاً (أكثر من 1 من 1,000 مريض وأقل من 1 من 100 مريض) هي:
- دوخة، نعاس، أرق، إرتباك، نوبات
- انخفاض ضغط الدم، انخفاض معدل نبضات القلب
- ضيق في التنفس، التهاب الحلق
- إمساك، عدوى فطرية بالفم، إسهال مرتبط بالمضاد الحيوي، قلس الحمض، جفاف الفم، عسر الهضم، فقدان الشهية
- احمرار الجلد
- تهيج وإفراز مهبلي
- آلام في البطن، تعب، عدوى فطرية، حمّى، وذمة/تورم، ألم في الصدر، تغير المذاق لطعم غير طبيعي
- تغيرات في نتائج بعض فحوصات البول والدم المختبرية
الآثار الجانبية التي تم الإبلاغ عنها بشكل نادر (أكثر من 1 من 10,000 مريض وأقل من 1 من 1,000 مريض) هي:
- انخفاض عدد كريات الدم البيضاء، انخفاض عدد الصفائح الدموية
- انخفاض سكر الدم
- تهيج، قلق، اكتئاب، رعاش
- عدم انتظام معدل نبضات القلب، ارتفاع ضغط الدم، نزيف، تسارع نبضات القلب
- احتقان الأنف، سعال، نزيف من الأنف، التهاب رئوي، أصوات تنفس غير طبيعية، صفير
- التهاب المرارة، صعوبة في البلع، سلس البراز، يرقان، اضطراب الكبد
- التهاب الجلد، عدوى فطرية بالجلد، تقشر الجلد، عدوى في الجروح بعد إجراء عملية
- تشنجات عضلية، ألم في الكتف
- التهاب المسالك البولية، اعتلال الكلى
- إجهاض، نزيف في الأعضاء التناسلية
- حساسية، شعور بالإعياء، التهاب الصفاق الحوضي، تغيرات في الجزء الأبيض من العين، إغماء.
الآثار الجانبية التي تم الإبلاغ عنها (غير معروف مدى شيوعها) منذ تسويق إيرتابينام هي:
- هلوسة
- انخفاض مستوى الوعي
- تغير الحالة العقلية (تتضمن العدوانية، الهذيان، التوهان، تغيرات في الحالة العقلية)
- حركات غير طبيعية
- ضعف العضلات
- اضطراب في المشي
- تلون الأسنان
كما تم الإبلاغ عن تغيرات في نتائج بعض فحوصات الدم المخبرية.
الأطفال والمراهقون (من 3 أشهر إلى 17 عاماً):
الآثار الجانبية الأكثر شيوعاً (أكثر من 1 من 100 مريض وأقل من 1 من 10 مرضى) هي:
- إسهال
- طفح ناتج عن الحفاضات
- ألم عند موضع التسريب
- تغيرات في عدد كريات الدم البيضاء
- تغيرات في فحوصات وظائف الكبد
الآثار الجانبية الأقل شيوعاً (أكثر من 1 من 1,000 مريض وأقل من 1 من 100 مريض) هي:
- صداع
- هبات ساخنة، ارتفاع ضغط الدم، بقع حمراء أو أرجوانية، مسطحة بحجم رأس الدبوس تحت الجلد
- براز عديم اللون، براز أسود شبيه بالقطران
- احمرار الجلد، طفح جلدي
- شعور بالحرقة، حكة، احمرار وسخونة عند موضع التسريب، احمرار عند موضع الحقن
- زيادة عدد الصفائح الدموية
- تغيرات في نتائج بعض فحوصات الدم المخبرية
الآثار الجانبية التي تم الإبلاغ عنها (غير معروف مدى شيوعها) منذ تسويق إيرتابينام هي:
- هلوسة
- تغير الحالة العقلية (تتضمن العدوانية
احفظ هذا الدواء بعيداً عن مرأى ومتناول الأطفال.
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المادة الفعّالة هي إيرتابينام الصوديوم. تحتوي كل زجاجة على ۱۰٤٦ ملغم إیرتابینام الصودیوم یكافئ ۱۰۰۰ ملغم إیرتابینام.
المواد الأخرى المستخدمة في التركيبة التصنيعية هي كربونات الصودیوم الھیدروجینیة وھیدروكسید الصودیوم.
إيرانزا 1000 ملغم مسحوق لتشكيل المركز ثم التخفيف قبل التسريب هو مسحوق مجفّد ذو لون أبيض مائل إلى الصفرة، خالٍ من موّلدات الحمّى ومعقم معبأ في زجاجات من النوع الأول حجمها 20 مللتر عديمة اللون وشفافة ومعقمة وخالية من موّلدات الحمّى معها سدادة مطاطية من الكلوروبوتيل وغطاء قابل للنزع من الألومنيوم.
حجم العبوة: 10 زجاجات.
اسم وعنوان مالك رخصة التسويق
شركة الجزيرة للصناعات الدوائية
طريق الخرج
صندوق بريد 106229
الرياض 11666، المملكة العربية السعودية
هاتف: 8107023 (11-966) +، 2142472 (11-966) +
فاكس: 2078170 (11-966) +
البريد الإلكتروني: jpimedical@hikma.com
الشركة المصنعة
شركة أسي إس دوبفار المساهمة
المنطقة الصناعية
64100 تيرامو
إيطاليا
للحصول على معلومات تتعلق بهذا الدواء، اتصل بالممثل المحلي للشركة مالكة رخصة التسويق على الرقم التالي:
· المملكة العربية السعودية
هاتف: 4173731 (11-966) +، فرعي: 1086
للإبلاغ عن الآثار الجانبية
تحدث إلى الطبيب، الصيدلي، أو الممرض إذا عانيت من أية آثار جانبية، بما فيها الآثار الجانبية التي لم يتم ذكرها في هذه النشرة. كما أنه يمكنك الإبلاغ عن هذه الآثار مباشرةً من خلال الاتصال بالجهات المذكورة أدناه. يساعد الإبلاغ عن الآثار الجانبية بتوفير معلومات مهمة عن مأمونية الدواء.
· المملكة العربية السعودية
المركز الوطني للتيقظ الدوائي
فاكس: 2057662 (11-966) +
رقم الهاتف: 2038222 (11-966) +، فرعي: 2317-2356-2340.
الرقم المجاني: 19999
البريد الإلكتروني: npc.drug@sfda.gov.sa
الموقع الإلكتروني: https://ade.sfda.gov.sa
· في بلدان مجلس التعاون الخليجي الأخرى
الرجاء الاتصال بالمؤسسات والهيئات الوطنية المختصة في كل دولة
Treatment
Eranza is indicated in paediatric patients (3 months to 17 years of age) and in adults for the treatment of the following infections when caused by bacteria known or very likely to be susceptible to ertapenem and when parenteral therapy is required (see sections 4.4 and 5.1):
- Intra-abdominal infections
- Community acquired pneumonia
- Acute gynaecological infections
- Diabetic foot infections of the skin and soft tissue (see section 4.4)
Prevention
Eranza is indicated in adults for the prophylaxis of surgical site infection following elective colorectal surgery (see section 4.4).
Consideration should be given to official guidance on the appropriate use of antibacterial agents
Posology
Treatment
Adults and adolescents (13 to 17 years of age): The dose of Eranza is 1000 mg given once a day by the intravenous route (see section 6.6).
Infants and children (3 months to 12 years of age): The dose of Eranza is 15 mg/kg given twice daily (not to exceed 1000 mg/day) by the intravenous route (see section 6.6).
Prevention
Adults: To prevent surgical site infections following elective colorectal surgery, the recommended dosage is 1000 mg administered as a single intravenous dose to be completed within 1 hour prior to the surgical incision.
Paediatric population
The safety and efficacy of ertapenem in children below 3 months of age have not yet been established.
No data are available.
Renal impairment
Eranza may be used for the treatment of infections in adult patients with mild to moderate renal impairment. In patients whose creatinine clearance is > 30 ml/min/1.73 m2, no dosage adjustment is necessary. There are inadequate data on the safety and efficacy of ertapenem in patients with severe renal impairment to support a dose recommendation. Therefore, ertapenem should not be used in these patients (see section 5.2). There are no data in children and adolescents with renal impairment.
Haemodialysis
There are inadequate data on the safety and efficacy of ertapenem in patients on haemodialysis to support a dose recommendation. Therefore, ertapenem should not be used in these patients.
Hepatic impairment
No dosage adjustment is recommended in patients with impaired hepatic function (see section 5.2).
Elderly
The recommended dose of Eranza should be administered, except in cases of severe renal impairment (see Renal impairment).
Method of administration
Intravenous administration: Eranza should be infused over a period of 30 minutes.
The usual duration of therapy with Eranza is 3 to 14 days but may vary depending on the type and severity of infection and causative pathogen(s). When clinically indicated, a switch to an appropriate oral antibacterial agent may be implemented if clinical improvement has been observed.
For instructions on preparation of the medicinal product before administration, see section 6.6.
Hypersensitivity
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. Before initiating therapy with ertapenem, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens (see section 4.3). If an allergic reaction to ertapenem occurs (see section 4.8), discontinue the therapy immediately. Serious anaphylactic reactions require immediate emergency treatment.
Superinfection
Prolonged use of ertapenem may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Antibiotic-associated colitis
Antibiotic-associated colitis and pseudomembranous colitis have been reported with ertapenem and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents. Discontinuation of therapy with Eranza and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
Seizures
Seizures have been reported during clinical investigation in adult patients treated with ertapenem (1000 mg once a day) during therapy or in the 14-day follow-up period. Seizures occurred most commonly in elderly patients and those with pre-existing central nervous system (CNS) disorders (e.g. brain lesions or history of seizures) and/or compromised renal function. Similar observations have been made in the post-marketing environment.
Concomitant use with valproic acid
The concomitant use of ertapenem and valproic acid/sodium valproate is not recommended (see section 4.5).
Sub-optimal exposure
Based on the data available it cannot be excluded that in the few cases of surgical interventions exceeding 4 hours, patients could be exposed to sub-optimal ertapenem concentrations and consequently to a risk of potential treatment failure. Therefore, caution should be exercised in such unusual cases.
Excipient
Eranza contains sodium. Eranza contains approximately 6.0 mEq (approximately 137 mg) of sodium per 1000 mg dose which should be taken into consideration by patients on a controlled sodium diet.
Considerations for use in particular populations
Experience in the use of ertapenem in the treatment of severe infections is limited. In clinical studies for the treatment of community-acquired pneumonia, in adults, 25 % of evaluable patients treated with ertapenem had severe disease (defined as pneumonia severity index > III). In a clinical study for the treatment of acute gynaecologic infections, in adults, 26 % of evaluable patients treated with ertapenem had severe disease (defined as temperature ≥ 39°C and/or bacteraemia); ten patients had bacteraemia. Of evaluable patients treated with ertapenem in a clinical study for the treatment of intra-abdominal infections, in adults, 30 % had generalized peritonitis and 39 % had infections involving sites other than the appendix including the stomach, duodenum, small bowel, colon, and gallbladder; there were limited numbers of evaluable patients who were enrolled with APACHE II scores ≥ 15 and efficacy in these patients has not been established.
The efficacy of ertapenem in the treatment of community acquired pneumonia due to penicillin-resistant Streptococcus pneumoniae has not been established.
Efficacy of ertapenem in the treatment of diabetic foot infections with concurrent osteomyelitis has not been established.
There is relatively little experience with ertapenem in children less than two years of age. In this age group, particular care should be taken to establish the susceptibility of the infecting organism(s) to ertapenem. No data are available in children under 3 months of age.
Interactions caused by inhibition of P-glycoprotein-mediated clearance or CYP-mediated clearance of medicinal products are unlikely (see section 5.2).
Decreases in valproic acid levels that may fall below the therapeutic range have been reported when valproic acid was co-administered with carbapenem agents. The lowered valproic acid levels can lead to inadequate seizure control; therefore, concomitant use of ertapenem and valproic acid/sodium valproate is not recommended and alternative antibacterial or anti-convulsant therapies should be considered.
Pregnancy
Pregnancy category B.
Adequate and well-controlled studies have not been performed in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo-foetal development, parturition or post-natal development. However, ertapenem should not be used during pregnancy unless the potential benefit outweighs the possible risk to the foetus.
Breast-feeding
Ertapenem is excreted in human milk. Because of the potential for adverse reactions on the infant, mothers should not breast-feed their infants while receiving ertapenem.
Fertility
There are no adequate and well-controlled studies regarding the effect of ertapenem use on fertility in men and women. Preclinical studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).
No studies on the effects on the ability to drive and use machines have been performed.
Eranza may influence patient's ability to drive and use machines. Patients should be informed that dizziness and somnolence have been reported with ertapenem (see section 4.8).
Summary of the safety profile
Adults
The total number of patients treated with ertapenem in clinical studies was over 2,200 of which over 2,150 received a 1000 mg dose of ertapenem. Adverse reactions (i.e. considered by the investigator to be possibly, probably, or definitely related to the medicinal product) were reported in approximately 20 % of patients treated with ertapenem. Treatment was discontinued due to adverse reactions in 1.3 % of patients. An additional 476 patients received ertapenem as a single 1000 mg dose prior to surgery in a clinical study for the prophylaxis of surgical site infections following colorectal surgery.
For patients who received only ertapenem, the most common adverse reactions reported during therapy plus follow-up for 14 days after treatment was stopped were: diarrhoea (4.8 %), infused vein complication (4.5 %) and nausea (2.8 %).
For patients who received only ertapenem, the most frequently reported laboratory abnormalities and their respective incidence rates during therapy plus follow-up for 14 days after treatment was stopped were: elevations in ALT (4.6 %), AST (4.6 %), alkaline phosphatase (3.8 %) and platelet count (3.0 %).
Paediatric population (3 months to 17 years of age):
The total number of patients treated with ertapenem in clinical studies was 384. The overall safety profile is comparable to that in adult patients. Adverse reactions (i.e. considered by the investigator to be possibly, probably, or definitely related to the medicinal product) were reported in approximately 20.8 % of patients treated with ertapenem. Treatment was discontinued due to adverse reactions in 0.5 % of patients.
For patients who received only ertapenem, the most common adverse reactions reported during therapy plus follow-up for 14 days after treatment was stopped were: diarrhoea (5.2 %) and infusion site pain (6.1 %).
For patients who received only ertapenem, the most frequently reported laboratory abnormalities and their respective incidence rates during therapy plus follow-up for 14 days after treatment was stopped were: decreases in neutrophil count (3.0 %), and elevations in ALT (2.9 %) and AST (2.8 %).
Tabulated list of adverse reactions
For patients who received only ertapenem, the following adverse reactions were reported during therapy plus follow-up for 14 days after treatment was stopped:
Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data).
Adults 18 years of age and older | Children and adolescents (3 months to 17 years of age) | |
Infections and infestations | Uncommon: Oral candidiasis, candidiasis, fungal infection, pseudomembranous enterocolitis, vaginitis Rare: Pneumonia, dermatomycosis, postoperative wound infection, urinary tract infection | |
Blood and lymphatic system disorders | Rare: Neutropenia, thrombocytopenia | |
Immune system disorders | Rare: Allergy Not known: Anaphylaxis including anaphylactoid reactions | |
Metabolism and nutrition disorders | Uncommon: Anorexia Rare: Hypoglycaemia | |
Psychiatric disorders | Uncommon: Insomnia, confusion Rare: Agitation, anxiety, depression Not known: Altered mental status (including aggression, delirium, disorientation, mental status changes) | Not known: Altered mental status (including aggression) |
Nervous system disorders | Common: Headache Uncommon: Dizziness, somnolence, taste perversion, seizure (see section 4.4) Rare: Tremor, syncope Not known: Hallucinations, depressed level of consciousness, dyskinesia, myoclonus, gait disturbance | Uncommon: Headache Not known: Hallucinations |
Eye disorders | Rare: Scleral disorder | |
Cardiac disorders | Uncommon: Sinus bradycardia Rare: Arrhythmia, tachycardia | |
Vascular disorders | Common: Infused vein complication, phlebitis/thrombophlebitis Uncommon: Hypotension Rare: Haemorrhage, increased blood pressure | Uncommon: Hot flush, hypertension |
Respiratory, thoracic and mediastinal disorders | Uncommon: Dyspnoea, pharyngeal discomfort Rare: Nasal congestion, cough, epistaxis, rales/rhonchi, wheezing | |
Gastrointestinal disorders | Common: Diarrhoea, nausea, vomiting Uncommon: Constipation, acid regurgitation, dry mouth, dyspepsia, abdominal pain Rare: Dysphagia, faecal incontinence, pelvic peritonitis Not known: teeth staining | Common: Diarrhoea Uncommon: Faeces discoloured, melaena |
Hepato-biliary disorders | Rare: Cholecystitis, jaundice, liver disorder | |
Skin and subcutaneous tissue disorders | Common: Rash, pruritus Uncommon: Erythema, urticaria Rare: Dermatitis, desquamation Not known: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) | Common: Diaper dermatitis Uncommon: Erythema, rash, petechiae |
Musculoskeletal and connective tissue disorders | Rare: Muscle cramp, shoulder pain Not known: Muscular weakness | |
Renal and urinary disorders | Rare: Renal insufficiency, acute renal insufficiency | |
Pregnancy, puerperium and perinatal conditions | Rare: Abortion | |
Reproductive system and breast disorders | Rare: Genital bleeding | |
General disorders and administration site conditions | Uncommon: Extravasation, asthenia/fatigue, fever, oedema/swelling, chest pain Rare: Injection-site induration, malaise | Common: Infusion site pain Uncommon: Infusion site burning, infusion site pruritus, infusion site erythema, injection site erythema, infusion site warmth |
Investigations | ||
Chemistry | Common: Elevations in ALT, AST, alkaline phosphatase Uncommon: Increases in total serum bilirubin, direct serum bilirubin, indirect serum bilirubin, serum creatinine, serum urea, serum glucose Rare: Decreases in serum bicarbonate, serum creatinine and serum potassium; increases in serum LDH, serum phosphorus, serum potassium | Common: Elevations in ALT and AST |
Haematology | Common: Elevation in platelet count Uncommon: Decreases in white blood cells, platelet count, segmented neutrophils, haemoglobin and haematocrit; increases in eosinophils, activated partial thromboplastin time, prothrombin time, segmented neutrophils and white blood cells Rare: Decrease in lymphocytes; increases in band neutrophils, lymphocytes, metamyelocytes, monocytes, myelocytes; atypical lymphocytes | Common: Decreases in neutrophil count Uncommon: Increases in platelet count, activated partial thromboplastin time, prothrombin time, decreases in haemoglobin |
Urinalysis | Uncommon: Increases in urine bacteria, urine white blood cells, urine epithelial cells and urine red blood cells; urine yeast present Rare: Increase in urobilinogen | |
Miscellaneous | Uncommon: Positive Clostridium difficile toxin |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
• Saudi Arabia
The National Pharmacovigilance Center (NPC)
Fax: + (966-11) 2057662
Call NPC at: + (966-11) 2038222, Exts: 2317-2356-2340.
SFDA Call Center: 19999
e-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa/
• Other GCC States
Please contact the relevant competent authorit
No specific information is available on the treatment of overdose with ertapenem. Overdosing of ertapenem is unlikely. Intravenous administration of ertapenem at a 3 g daily dose for 8 days to healthy adult volunteers did not result in significant toxicity. In clinical studies in adults inadvertent administration of up to 3 g in a day did not result in clinically important adverse reactions. In paediatric clinical studies, a single intravenous (IV) dose of 40 mg/kg up to a maximum of 2 g did not result in toxicity.
However, in the event of an overdose, treatment with Eranza should be discontinued and general supportive treatment given until renal elimination takes place.
Ertapenem can be removed to some extent by haemodialysis (see section 5.2); however, no information is available on the use of haemodialysis to treat overdose.
General properties
Pharmacotherapeutic group: Antibacterials for systemic use, carbapenems, ATC code: J01DH03
Mechanism of action
Ertapenem inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). In Escherichia coli, affinity is strongest to PBPs 2 and 3.
Pharmacokinetic/Pharmacodynamic (PK/PD) relationship
Similar to other beta-lactam antimicrobial agents, the time that the plasma concentration of ertapenem exceeds the MIC of the infecting organism has been shown to best correlate with efficacy in pre-clinical PK/PD studies.
Mechanism of resistance
For species considered susceptible to ertapenem, resistance was uncommon in surveillance studies in Europe. In resistant isolates, resistance to other antibacterial agents of the carbapenem class was seen in some but not all isolates. Ertapenem is effectively stable to hydrolysis by most classes of beta-lactamases, including penicillinases, cephalosporinases and extended spectrum beta-lactamases, but not metallo-beta-lactamases.
Methicillin-resistant staphylococci and enterococci are resistant to ertapenem, owing to PBP target insensitivity; P. aeruginosa and other non-fermentative bacteria are generally resistant, probably owing to limited penetration and to active efflux.
Resistance is uncommon in Enterobacteriaceae and ertapenem is generally active against those with extended-spectrum beta-lactamases (ESBLs). Resistance can however be observed when ESBLs or other potent beta-lactamases (e.g. AmpC types) are present in conjunction with reduced permeability, arising by the loss of one or more outer membrane porins, or with up-regulated efflux. Resistance can also arise via the acquisition of betalactamases with significant carbapenem-hydrolysing activity (e.g. IMP and VIM metallo-beta-lactamases or KPC types), though these are rare.
The mechanism of action of ertapenem differs from that of other classes of antibiotics, such as quinolones, aminoglycosides, macrolides and tetracyclines. There is no target-based cross-resistance between ertapenem and these substances. However, micro-organisms may exhibit resistance to more than one class of antibacterial agents when the mechanism is, or includes, impermeability to some compounds and/or an efflux pump.
Breakpoints
The EUCAST MIC breakpoints are as follows:
- Enterobacteriaceae: S≤ 0.5 mg/l and R > 1 mg/l
- Streptococcus A,B,C,G: S≤ 0.5 mg/l and R > 0.5 mg/l
- Streptococcus pneumoniae: S ≤ 0.5 mg/l and R > 0.5 mg/l
- Haemophilus influenzae: S ≤ 0.5 mg/l and R > 0.5 mg/l
- M. catarrhalis: S ≤ 0.5 mg/l and R > 0.5 mg/l
- Gram negative anaerobes: S ≤ 1mg/l and R > 1 mg/l
- Non-species related breakpoints: S ≤ 0.5 mg/l and R > 1 mg/l
(NB: Susceptibility of staphylococci to ertapenem is inferred from the methicillin susceptibility)
The prescribers are informed that local MIC breakpoints, if available, should be consulted.
Microbiological susceptibility
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. Localised clusters of infections due to carbapenem-resistant organisms have been reported in the European Union. The information below gives only approximate guidance on the probability as to whether the micro-organism will be susceptible to ertapenem or not.
Commonly susceptible species: |
Gram-positive aerobes: Methicillin-susceptible-staphylococci (including Staphylococcus aureus)* Streptococcus agalactiae* Streptococcus pneumoniae*† Streptococcus pyogenes |
Gram-negative aerobes: Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Escherichia coli* Haemophilus influenzae* Haemophilus parainfluenzae Klebsiella oxytoca Klebsiella pneumoniae* Moraxella catarrhalis* Morganella morganii Proteus mirabilis* Proteus vulgaris Serratia marcescens |
Anaerobes: Clostridium species (excluding C. difficile)* Eubacterium species* Fusobacterium species* Peptostreptococcus species* Porphyromonas asaccharolytica* Prevotella species* |
Species for which acquired resistance may be a problem: |
Gram-positive aerobes: Methicillin-resistant staphylococci +# |
Anaerobes: Bacteroides fragilis and species in the B. fragilis Group* |
Inherently resistant organisms: |
Gram-positive aerobes: Corynebacterium jeikeium Enterococci including Enterococcus faecalis and Enterococcus faecium |
Gram-negative aerobes: Aeromonas species Acinetobacter species Burkholderia cepacia Pseudomonas aeruginosa Stenotrophomonas maltophilia |
Anaerobes: Lactobacillus species |
Others: Chlamydia species Mycoplasma species Rickettsia species Legionella species |
* Activity has been satisfactorily demonstrated in clinical studies.
† The efficacy of ertapenem in the treatment of community acquired pneumonia due to penicillin-resistant Streptococcus pneumoniae has not been established.
+ frequency of acquired resistance > 50 % in some Member States
# Methicillin-resistant staphylococci (including MRSA) are always resistant to betalactams.
Information from clinical studies
Efficacy in Paediatric Studies
Ertapenem was evaluated primarily for paediatric safety and secondarily for efficacy in randomised comparative, multicentre studies in patients 3 months to 17 years of age.
The proportion of patients with a favourable clinical response assessment at post-treatment visit in the clinical MITT population is shown below:
Disease Stratum† | Age Stratum | Ertapenem | Ceftriaxone | ||
n/m | % | n/m | % | ||
Community Acquired Pneumonia (CAP) | 3 to 23 months | 31/35 | 88.6 | 13/13 | 100.0 |
2 to 12 years | 55/57 | 96.5 | 16/17 | 94.1 | |
13 to 17 years | 3/3 | 100.0 | 3/3 | 100.0 | |
Disease Stratum | Age Stratum | Ertapenem | Ticarcillin/clavulanate | ||
n/m | % | n/m | % | ||
Intra-abdominal Infections (IAI) | 2 to 12 years | 28/34 | 82.4 | 7/9 | 77.8 |
13 to 17 years | 15/16 | 93.8 | 4/6 | 66.7 | |
Acute Pelvic Infections (API) | 13 to 17 years | 25/25 | 100.0 | 8/8 | 100.0 |
† This includes 9 patients in the ertapenem group (7 CAP and 2 IAI), 2 patients in the ceftriaxone group (2 CAP), and 1 patient with IAI in the ticarcillin/clavulanate group with secondary bacteraemia at entry into the study.
Plasma concentrations
Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 1000 mg dose in healthy young adults (25 to 45 years of age) were 155 micrograms/ml (Cmax) at 0.5 hour post-dose (end of infusion), 9 micrograms/ml at 12 hour post-dose, and 1 microgram/ml at 24 hour post-dose.
Area under the plasma concentration curve (AUC) of ertapenem in adults increases nearly dose-proportionally over the 0.5 to 2 g dose range.
There is no accumulation of ertapenem in adults following multiple intravenous doses ranging from 0.5 to 2 g daily.
Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 15 mg/kg (up to a maximum dose of 1000 mg) dose in patients 3 to 23 months of age were 103.8 micrograms/ml (Cmax) at 0.5 hour post-dose (end of infusion), 13.5 micrograms/ml at 6 hour post-dose, and 2.5 micrograms/ml at 12 hour post-dose.
Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 15 mg/kg (up to a maximum dose of 1000 mg) dose in patients 2 to 12 years of age were 113.2 micrograms/ml (Cmax) at 0.5 hour post-dose (end of infusion), 12.8 micrograms/ml at 6 hour post-dose, and 3.0 micrograms/ml at 12 hour post-dose.
Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 20 mg/kg (up to a maximum dose of 1000 mg) dose in patients 13 to 17 years of age were 170.4 micrograms/ml (Cmax) at 0.5 hour post-dose (end of infusion), 7.0 micrograms/ml at 12 hour post-dose, and 1.1 microgram/ml at 24 hour post-dose.
Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 1000 mg dose in three patients 13 to 17 years of age were 155.9 micrograms/ml (Cmax) at 0.5 hour post-dose (end of infusion), and 6.2 micrograms/ml at 12 hour post-dose.
Distribution
Ertapenem is highly bound to human plasma proteins. In healthy young adults (25 to 45 years of age), the protein binding of ertapenem decreases, as plasma concentrations increase, from approximately 95 % bound at an approximate plasma concentration of < 50 micrograms/ml to approximately 92 % bound at an approximate plasma concentration of 155 micrograms/ml (average concentration achieved at the end of infusion following 1000 mg intravenously).
The volume of distribution (Vdss) of ertapenem in adults is approximately 8 litres (0.11 litre/kg) and approximately 0.2 litre/kg in paediatric patients 3 months to 12 years of age and approximately 0.16 litre/kg in paediatric patients 13 to 17 years of age.
Concentrations of ertapenem achieved in adult skin blister fluid at each sampling point on the third day of 1000 mg once daily intravenous doses showed a ratio of AUC in skin blister fluid: AUC in plasma of 0.61.
In-vitro studies indicate that the effect of ertapenem on the plasma protein binding of highly protein bound medicinal products (warfarin, ethinyl estradiol, and norethindrone) was small. The change in binding was < 12 % at peak plasma ertapenem concentration following a 1000 mg dose. In vivo, probenecid (500 mg every 6 hours) decreased the bound fraction of ertapenem in plasma at the end of infusion in subjects administered a single 1000 mg intravenous dose from approximately 91 % to approximately 87 %. The effects of this change are anticipated to be transient. A clinically significant interaction due to ertapenem displacing another medicinal product or another medicinal product displacing ertapenem is unlikely.
In-vitro studies indicate that ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine and that ertapenem is not a substrate for P-glycoprotein-mediated transport.
Biotransformation
In healthy young adults (23 to 49 years of age), after intravenous infusion of radiolabelled 1000 mg ertapenem, the plasma radioactivity consists predominantly (94 %) of ertapenem. The major metabolite of ertapenem is the ring-opened derivative formed by dehydropeptidase-I-mediated hydrolysis of the beta-lactam ring.
In-vitro studies in human liver microsomes indicate that ertapenem does not inhibit metabolism mediated by any of the six major CYP isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4.
Elimination
Following administration of a 1000 mg radiolabelled intravenous dose of ertapenem to healthy young adults (23 to 49 years of age), approximately 80 % is recovered in urine and 10 % in faeces. Of the 80 % recovered in urine, approximately 38 % is excreted as unchanged ertapenem and approximately 37 % as the ring-opened metabolite.
In healthy young adults (18 to 49 years of age) and patients 13 to 17 years of age given a 1000 mg intravenous dose, the mean plasma half-life is approximately 4 hours. The mean plasma half-life in children 3 months to 12 years of age is approximately 2.5 hours. Average concentrations of ertapenem in urine exceed 984 micrograms/ml during the period 0 to 2 hours post-dose and exceed 52 micrograms/ml during the period 12 to 24 hours post-administration.
Special populations
Gender
The plasma concentrations of ertapenem are comparable in men and women.
Elderly
Plasma concentrations following a 1000 mg and 2000 mg intravenous dose of ertapenem are slightly higher (approximately 39 % and 22 %, respectively) in healthy elderly adults (≥ 65 years) relative to young adults (< 65 years). In the absence of severe renal impairment, no dosage adjustment is necessary in elderly patients.
Paediatric population
Plasma concentrations of ertapenem are comparable in paediatric patients 13 to 17 years of age and adults following a 1000 mg once daily intravenous dose.
Following the 20 mg/kg dose (up to a maximum dose of 1000 mg), the pharmacokinetic parameter values in patients 13 to 17 years of age were generally comparable to those in healthy young adults. To provide an estimate of the pharmacokinetic data if all patients in this age group were to receive a 1000 mg dose, the pharmacokinetic data were calculated adjusting for a 1000 mg dose, assuming linearity. A comparison of results show that a 1000 mg once daily dose of ertapenem achieves a pharmacokinetic profile in patients 13 to 17 years of age comparable to that of adults. The ratios (13 to 17 years/Adults) for AUC, the end of infusion concentration and the concentration at the midpoint of the dosing interval were 0.99, 1.20, and 0.84, respectively.
Plasma concentrations at the midpoint of the dosing interval following a single 15 mg/kg intravenous dose of ertapenem in patients 3 months to 12 years of age are comparable to plasma concentrations at the midpoint of the dosing interval following a 1000 mg once daily intravenous dose in adults (see Plasma concentrations). The plasma clearance (ml/min/kg) of ertapenem in patients 3 months to 12 years of age is approximately 2-fold higher as compared to that in adults. At the 15 mg/kg dose, the AUC value and plasma concentrations at the midpoint of the dosing interval in patients 3 months to 12 years of age were comparable to those in young healthy adults receiving a 1000 mg intravenous dose of ertapenem.
Hepatic impairment
The pharmacokinetics of ertapenem in patients with hepatic impairment have not been established. Due to the limited extent of hepatic metabolism of ertapenem, its pharmacokinetics are not expected to be affected by hepatic impairment. Therefore, no dosage adjustment is recommended in patients with hepatic impairment.
Renal impairment
Following a single 1000 mg intravenous dose of ertapenem in adults, AUCs of total ertapenem (bound and unbound) and of unbound ertapenem are similar in patients with mild renal impairment (Clcr 60 to 90 ml/min/1.73 m2) compared with healthy subjects (ages 25 to 82 years). AUCs of total ertapenem and of unbound ertapenem are increased in patients with moderate renal impairment (Clcr 31 to 59 ml/min/1.73 m2) approximately 1.5-fold and 1.8-fold, respectively, compared with healthy subjects. AUCs of total ertapenem and of unbound ertapenem are increased in patients with severe renal impairment (Clcr 5 to 30 ml/min/1.73 m2) approximately 2.6-fold and 3.4-fold, respectively, compared with healthy subjects. AUCs of total ertapenem and of unbound ertapenem are increased in patients who require haemodialysis approximately 2.9-fold and 6.0-fold, respectively, between dialysis sessions, compared with healthy subjects. Following a single 1000 mg intravenous dose given immediately prior to a haemodialysis session, approximately 30 % of the dose is recovered in the dialysate. There are no data in paediatric patients with renal impairment.
There are inadequate data on the safety and efficacy of ertapenem in patients with advanced renal impairment and patients who require haemodialysis to support a dose recommendation. Therefore, ertapenem should not be used in these patients.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety, pharmacology, repeated-dose toxicity, genotoxicity and toxicity to reproduction and development. Decreased neutrophil counts, however, occurred in rats that received high doses of ertapenem, which was not considered a significant safety issue.
Long-term studies in animals to evaluate the carcinogenic potential of ertapenem have not been performed.
- Sodium hydrogen carbonate
- Sodium hydroxide.
Do not use solvents or infusion fluids containing dextrose for reconstitution or administration of ertapenem.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Do not store above 25°C.
Store in the original package.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
20 ml colorless clear sterile pyrogen-free type I glass vials with chlorobutyl rubber stoppers and aluminum flip-off overseals.
Pack size: 10 vials.
Instructions for use:
For single use only.
Reconstituted solutions should be diluted in sodium chloride 9 mg/ml (0.9 %) solution immediately after preparation.
Preparation for intravenous administration:
Eranza must be reconstituted and then diluted prior to administration.
Adults and adolescents (13 to 17 years of age)
Reconstitution
Reconstitute the contents of a 1000 mg vial of Eranza with 10 ml of sterile water for injection or sodium chloride 9 mg/ml (0.9 %) solution to yield a reconstituted solution of approximately 100 mg/ml. Shake well to dissolve. (See section 6.4).
Dilution
· For a 50 ml bag of diluent: For a 1000 mg dose, immediately transfer contents of the reconstituted vial to a 50 ml bag of sodium chloride 9 mg/ml (0.9 %) solution; or
· For a 50 ml vial of diluent: For a 1000 mg dose, withdraw 10 ml from a 50 ml vial of sodium chloride 9 mg/ml (0.9 %) solution and discard. Transfer the contents of the reconstituted 1000 mg vial of Eranza to the 50 ml vial of sodium chloride 9 mg/ml (0.9 %) solution.
Infusion
Infuse over a period of 30 minutes.
Children (3 months to 12 years of age)
Reconstitution
Reconstitute the contents of a 1000 mg vial of Eranza with 10 ml of sterile water for injection or sodium chloride 9 mg/ml (0.9 %) solution to yield a reconstituted solution of approximately 100 mg/ml. Shake well to dissolve. (See section 6.4.)
Dilution
· For a bag of diluent: Transfer a volume equal to 15 mg/kg of body weight (not to exceed 1000 mg/day) to a bag of sodium chloride 9 mg/ml (0.9 %) solution for a final concentration of 20 mg/ml or less; or
· For a vial of diluent: Transfer a volume equal to 15 mg/kg of body weight (not to exceed 1000 mg/day) to a vial of sodium chloride 9 mg/ml (0.9 %) solution for a final concentration of 20 mg/ml or less.
Infusion
Infuse over a period of 30 minutes.
Compatibility of Eranza with intravenous solutions containing heparin sodium and potassium chloride has been demonstrated.
The reconstituted solutions should be inspected visually for particulate matter and discoloration prior to administration, whenever the container permits. Solutions of Eranza range from colourless to pale yellow. Variations of colour within this range do not affect potency.
Any unused product or waste material should be disposed of in accordance with local requirements.
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