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نشرة الممارس الصحي نشرة معلومات المريض بالعربية نشرة معلومات المريض بالانجليزية صور الدواء بيانات الدواء
  SFDA PIL (Patient Information Leaflet (PIL) are under review by Saudi Food and Drug Authority)

What Refixia® is

Refixia® contains the active substance nonacog beta pegol and is a long-acting pegylated recombinant coagulation factor IX product. Factor IX is a protein found naturally in the blood and helps to stop bleeding.

 

What Refixia® is used for

Refixia® is used to treat and prevent bleeding episodes in previously treated patients with hemophilia B (inborn factor IX deficiency).

In patients with hemophilia B, factor IX is missing or does not work properly. Refixia® replaces this faulty or missing factor IX and helps the blood to form clots at the site of bleeding. When you bleed, Refixia® is activated in the blood and forms the naturally occurring factor IX.


Do not use Refixia®

·         If you are allergic to any of the ingredients in Refixia®. (listed in section 6 Contents of the pack and other information).

·         If you have a hypersensitivity to hamster proteins.

Do not use Refixia® if any of the above apply to you. If you are not sure, talk to your doctor before using this medicine.

 

Warnings and precautions

 

Allergic reactions and development of inhibitors

There is a rare risk that you may experience a sudden and severe allergic reaction (e.g. anaphylactic reaction) to Refixia®. Stop the injection and contact your doctor or an emergency unit immediately if you have signs of an allergic reaction such as rash, hives, weals, itching on large areas of skin, redness and/or swelling of lips, tongue, face or hands, difficulty in swallowing or breathing, shortness of breath, wheezing, tightness of the chest, pale and cold skin, fast heartbeat, and/or dizziness.

Your doctor may need to treat you promptly for these reactions. Your doctor may also do a blood test to check if you have developed factor IX inhibitors (neutralising antibodies) against your medicine, as inhibitors may develop together with allergic reactions. If you have such antibodies, you may be at an increased risk of sudden and severe allergic reactions (e.g. anaphylactic reaction) during future treatment with factor IX.

Because of the risk of allergic reactions with factor IX, your initial treatment with Refixia® should be given in a medical clinic or in the presence of health care professionals where proper medical care for allergic reactions can be provided if needed.

Talk to your doctor immediately if your bleeding does not stop as expected or if you have to significantly increase your usage of Refixia® in order to stop a bleed. Your doctor will do a blood test to check if you have developed inhibitors (neutralising antibodies) against Refixia®. The risk for developing inhibitors is highest if you have not been treated with factor IX medicines before i.e. for small children.

 

Blood clots

Tell your doctor, if any of the following apply to you as there is an increased risk of blood clots during treatment with Refixia®:

·         You have recently had surgery

·         You suffer from other serious illness e.g. liver disease, heart disease, or cancer

 

Kidney disease (nephrotic syndrome)

In hemophilia B patients with a history of factor IX inhibitors and allergic reactions, there is a small risk of developing a specific kidney disease called “nephrotic syndrome” after the use of high doses of factor IX.

 

 

Other medicines and Refixia®

Tell your doctor or pharmacist if you

·         have other illnesses,

·         have allergies, or

·         are taking other medicines (including those you bought yourself!) or are using them externally!

 

Pregnancy and breast-feeding

If you are pregnant or breastfeeding, think that you may be pregnant or are planning to become pregnant, talk to your doctor before using Refixia®.

 

 

 

Driving and using machines

Refixia® has no effect on the ability to drive and use machines.

 

Refixia® contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per vial.


Treatment with Refixia® will be started by a doctor who is experienced in the treatment of patients with hemophilia B. Always use Refixia® exactly as your doctor has told you. Please check with your doctor if you are not sure how to use Refixia®.

Your doctor will calculate your dose for you. Your dose will depend on your weight and the purpose for which you are using the medicine.

Do not change the prescribed dosage on your own. If you think the medicine is too weak or too strong, talk to your doctor or pharmacist.

 

Prevention of bleeding

The dose of Refixia® is 40 international units (IU) per kg body weight. It is given in one injection per week.

 

Treatment of bleeding

The dose of Refixia® is 40 international units (IU) per kg body weight. Depending on the severity and location of the bleeding, you may also need a higher dose (80 IU per kg) or an additional injection/additional injections. Discuss with your doctor the dose and number of injections you need.

 

Use in children and Adolescents

Refixia® can be used in children of all ages. The dosage in children and adolescents is the same as that in adults.

 

How Refixia® is given

Refixia® is given as an injection into a vein. See Instructions on how to use Refixia® for more information.

 

If you use more Refixia® than you should

If you use more Refixia® than you should, please contact your doctor.

Contact your doctor immediately if you need to use significantly more Refixia® to stop a bleed. See “Allergic reactions and development of antibodies” for more information.

 

If you forget to use Refixia®

If you forget a dose, inject the missed dose as soon as you remember. Do not inject a double dose to make up for a forgotten dose. If you are in doubt contact your doctor.

 

If you stop using Refixia®

If you stop using Refixia® you may no longer be protected against bleeding or a current bleed may not stop. Do not stop using Refixia® without talking to your doctor.

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

 


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

Allergic reactions (hypersensitivity) may occur when using this medicine.

If sudden and severe allergic reactions (e.g., anaphylactic reactions) occur, the injection must be stopped

immediately. You must immediately contact your doctor or an emergency department if you experience

early signs of an allergic reaction, such as:

·         difficulty swallowing or breathing

·         shortness of breath or wheezing

·         feeling of tightness in the chest

·         redness and/or swelling of the lips, tongue, face or hands

·         skin rash, hives, welts, or generalized itching

·         pale and cold skin, fast heartbeat and/or dizziness (low blood pressure)

 

Inhibitors (antibodies that neutralize the activity) have occurred in connection with severe and sudden

allergic reactions (e.g., anaphylactic reaction).

The following side effects have been observed with Refixia®:

 

Common side effects (up to 1 in 10)

·         itching (pruritus)

·         skin reactions at the injection site.

 

Uncommon side effects (up to 1 in 100)

·         allergic reactions (hypersensitivity).

 

Side effects with unknown frequency (how often these side effects occur is unknown)

·         anaphylactic reactions

·         development of antibodies (inhibitors).

 

 

Reporting of side effects

If you notice any side effects not described here, you should tell your doctor or pharmacist.


·         Keep Refixia® out of the sight and reach of children.

·         Do not use Refixia® after the expiration date which is indicated on the outer box, vial and pre-filled syringe label after “EXP”. The date printed refers to the last day of that month.

·         Store in the original package to protect contents from light.

·         Store in the refrigerator (2-8°C).

·         Do not freeze.

 

Before the Refixia® powder is prepared for use, it can be stored at room temperature (up to 30°C) for a period of no more than 6 months. Please note the date you are starting to store Refixia® at room temperature, on the outer box. Do not return Refixia® to the refrigerator after you have already stored it at room temperature.

Once you have prepared Refixia® for use, it should be used immediately. If you cannot use the prepared Refixia® solution immediately, the vial can be stored at room temperature (up to 30°C) for no more than 4 hours or in the refrigerator at 2-8°C for no more than 24 hours. If it is not used immediately, the medicine may no longer be sterile and could cause infection.

The powder in the vial must be white or slightly yellowish. Do not use the powder if there is discoloration.

The prepared solution must be clear and colorless. Do not use this product if you notice that it is cloudy or contains visible particles.

Never dispose of medicinal products via wastewater or household waste. Ask your pharmacist how to dispose of any medicine you are no longer using. These measures will help to protect the environment.

Your doctor or pharmacist can give you further information based on the detailed prescribing information.

 


What Refixia® contains

Active ingredient: nonacog beta pegol (pegylated human coagulation factor IX (rDNA)). As specified by

the manufacturer, each vial of Refixia® contains 500 IU, 1000 IU or 2000 IU nonacog beta pegol.

Other ingredients: sodium chloride, sucrose, polysorbate 80, histidine, mannitol, sodium hydroxide and

hydrochloric acid.

Solvents: histidine, water for injection, sodium hydroxide and hydrochloric acid.

After preparation with the provided solvent (histidine solution), the prepared solution for injection contains 125 lU/mL, 250 lU/mL or 500 lU/mL nonacog beta pegol (based on the strength of nonacog beta pegol, i.e., 500 IU, 1,000 IU or 2,000 IU).


What Refixia® looks like and contents of the pack • Refixia® is provided as a powder and solvent for solution for injection (500 IU, 1000 IU or 2000 IU powder in a vial and 4 ml solvent in a pre-filled syringe, a plunger rod with a vial adapter – pack size of 1). • The powder is white to off-white and the solvent is clear and colourless.

Marketing authorisation holder and manufacturer
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd, Denmark


Leaflet revised date: August/2017
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

ما هو ريفكسيا™

يحتوي ريفكسيا™ على المادة الفعالة ‏‫نوناكوج بيتا بيجول، وهو عامل تجلط مؤتلف طويل المفعول مرتبط بعامل التخثر التاسع. العامل التاسع عبارة عن بروتين موجود بشكلٍ طبيعي في الدم ويساعد على وقف النزيف.

 

دواعي استخدام ريفكسيا™

يُستخدم ريفكسيا™ لعلاج ومنع نوبات النزيف لدى المرضى الذين سبق علاجهم من مرض الهيموفيليا ب (نقص وراثي في العامل التاسع).

يعاني مرضى الهيموفيليا ب، من عدم وجود العامل التاسع لتخثر الدم أو من عدم أدائه لوظائفه كما ينبغي. يحل ريفكسيا™محل هذا العامل التاسع الذي به خلل أو غير الموجود ويساعد الدم على تكوين تخثرات في موضع النزيف. وعندما تنزف، ينشط ريفكسيا™ في الدم ويُشكل العامل التاسع الذي ينشأ طبيعيًا.

لا تستخدم ريفكسيا™

·         إذا كنت تعاني من حساسية تجاه أي من مكونات ريفكسيا™ (الواردة في القسم 6 محتويات العبوة ومعلومات أخرى).

·         إذا كنت تعاني من فرط الحساسية تجاه بروتينات الهامستر.

لا تستخدم ريفكسيا™ إذا انطبق عليك أي مما سبق. وإذا لم تكن متأكدً، فتحدّث مع طبيبك قبل استخدام هذا الدواء.

 

تحذيرات واحتياطات

 

ردود الفعل التحسسية وتكوّن المثبطات

هناك خطر نادر يتمثل في احتمال تعرضك لرد فعل تحسسي مفاجئ وشديد (على سبيل المثال رد فعل تأقي) تجاه ريفكسيا™. أوقف الحقن واتصل بطبيبك أو وحدة الطوارئ على الفور إذا كنت تعاني من علامات الإصابة برد فعل تحسسي مثل الطفح الجلدي، والشرى، والانتبار، والحكة في مناطق كبيرة من الجلد، واحمرار و/أو تورم الشفاه، أو اللسان، أو الوجه أو اليدين، وصعوبة في البلع أو التنفس، وضيق في التنفس، وأزيز، وضيق في الصدر، وشحوب وبرودة في الجلد، وسرعة ضربات القلب، و/أو الدوار.

قد يحتاج طبيبك إلى علاجك على الفور من ردود الفعل هذه. قد يُجري طبيبك أيضًا فحصًا للدم للتحقق مما إذا كان قد تكوّنت لديك مثبطات العامل التاسع (الأجسام المضادة المعادلة) تجاه الدواء الخاص بك، حيث قد تتكوّن المثبطات مع ردود الفعل التحسسية. إذا كانت لديك مثل هذه الأجسام المضادة، فقد تكون أكثر عرضة لخطر ردود الفعل التحسسية المفاجئة والشديدة (على سبيل المثال رد فعل تأقي) أثناء العلاج في المستقبل بالعامل التاسع.

بسبب خطر الإصابة بردود الفعل التحسسية مع العامل التاسع، ينبغي أن تُعطى علاجك الأولي باستخدام ريفكسيا™ في عيادة طبية أو في وجود متخصصي الرعاية الصحية، بحيث يمكن توفير الرعاية الطبية المناسبة في حالة حدوث ردود الفعل التحسسية إذا لزم الأمر.

تحدّث إلى طبيبك على الفور إذا كان النزيف لديك لا يتوقف بالشكل المتوقع أو إذا كان يتعيّن عليك زيادة استخدامك لدواء ريفكسيا™ بشكل كبير من أجل إيقاف النزيف. سيجري طبيبك فحصًا للدم للتحقق مما إذا كان قد تكوّنت لديك مثبطات (الأجسام المضادة المعادلة) تجاه ريفكسيا™. يكون خطر تكوّن المثبطات أعلى إذا لم تكن قد تم علاجك بأدوية العامل التاسع من قبل، أي للأطفال الصغار.

 

الجلطات الدموية

أخبر طبيبك إذا انطبق عليك أي مما يلي حيث يوجد خطر متزايد يتمثل في الإصابة بجلطات دموية أثناء العلاج باستخدام ريفكسيا™:

·         أجريت مؤخرًا عملية جراحية

·         كنت تعاني من مرض خطير آخر على سبيل المثال مرض بالكبد، أو مرض بالقلب، أو السرطان

 

مرض الكلى (المتلازمة الكلوية)

بالنسبة لمرضى الهيموفيليا ب الذين لديهم تاريخ من مثبطات العامل التاسع وردود فعل تحسسية، هناك خطر ضئيل من الإصابة بمرض كلوي معيّن يسمى "المتلازمة الكلوية" بعد استخدام جرعات عالية من العامل التاسع.

 

 

الأدوية الأخرى وريفكسيا™

أخبر طبيبك أو الصيدلي إذا كنت

·         تعاني من أمراض أخرى، أو

·         تعاني من حساسية، أو

·         تتناول أدوية أخرى (بما في ذلك تلك التي اشتريتها بنفسك!) أو تستخدمها خارجيًا!

 

الحمل والرضاعة الطبيعية

إذا كنتِ حاملًا أو مرضعة، أو إذا كنتِ تظنين أنكِ قد تكوني حاملا أو تخططين للحمل، فاستشيري طبيبك قبل استخدام ريفكسيا™.

 

 

قيادة المركبات واستخدام الآلات

لا يوجد تأثير لدواء ريفكسيا™ على القدرة على القيادة واستخدام الآلات.

 

يحتوي ريفكسيا™ على الصوديوم

يحتوي هذا الدواء على أقل من 1 مللي مول صوديوم (23 ملغ) لكل قنينة.

https://localhost:44358/Dashboard

سيبدأ العلاج باستخدام ريفكسيا من قبل طبيب خبير في علاج المرضى الذين يعانون من الهيموفيليا ب. استخدم ريفكسيا دائمًا كما أخبرك طبيبك بالضبط. يُرجى مراجعة طبيبك إذا كنت غير متأكد من كيفية استخدام ريفكسيا.

سيحسب طبيبك الجرعة التي تناسبك. ستعتمد جرعتك على وزنك والغرض الذي تستخدم الدواء من أجله.

لا تغيّر الجرعة الموصوفة من تلقاء نفسك. إذا كنت تعتقد أن الدواء ضعيف جدًا أو قوي جدًا، فتحدث مع طبيبك أو الصيدلي.

 

منع النزيف

جرعة ريفكسيا™ عبارة عن 40 وحدة دولية (IU) لكل كجم من وزن الجسم. ويُعطى في حقنة واحدة في الأسبوع.

 

علاج النزيف

جرعة ريفكسيا™ عبارة عن 40 وحدة دولية (IU) لكل كجم من وزن الجسم. اعتمادًا على شدة و موضع النزيف، قد تحتاج أيضًا إلى جرعة أعلى (80 وحدة دولية لكل كجم) أو حقنة إضافية/حقن إضافية. ناقش مع طبيبك الجرعة وعدد الحُقن التي تحتاجها.

 

الاستخدام لدى الأطفال والمراهقين

يمكن استخدام ريفكسيا™ لدى الأطفال من جميع الأعمار. تعد جرعة الأطفال والمراهقين نفس الجرعة المُستخدمة لدى البالغين.

 

كيفية إعطاء ريفكسيا™

يُعطى ريفكسيا™ كحقنة في الوريد. راجع تعليمات كيفية استخدام ريفكسيا™ للحصول على مزيد من المعلومات.

 

في حالة استخدام كمية أكبر مما ينبغي من ريفكسيا™

في حالة استخدام كمية أكبر مما ينبغي من ريفكسيا™، يُرجى الاتصال بطبيبك.

اتصل بطبيبك على الفور إذا كنت بحاجة إلى استخدام المزيد من ريفكسيا™ لوقف النزيف. راجع "ردود الفعل التحسسية وتكوّن الأجسام المضادة" لمزيد من المعلومات.

 

في حالة نسيان استخدام ريفكسيا™

في حالة نسيان جرعة ما، احقن الجرعة الفائتة حالما تتذكرها. لا تحقن جرعة مضاعفة لتعويض الجرعة المنسية. اتصل بطبيبك في حالة الشك.

 

في حالة التوقف عن استخدام ريفكسيا™

في حالة التوقف عن استخدام ريفكسيا™، فقد لا تظل محميًا من النزيف أو قد لا يتوقف النزيف الحالي. لا تتوقف عن استخدام ريفكسيا™ دون التحدُّث إلى طبيبك.

إذا كانت لديك أي أسئلة أخرى حول استخدام هذا الدواء، فاسأل طبيبك.

 

مثل كل الأدوية، يمكن أن يسبب هذا الدواء آثارًا جانبية، على الرغم من ذلك لا يُصاب جميع المستخدمين بها.

قد تحدث ردود فعل تحسسية (فرط الحساسية) عند استخدام هذا الدواء.

في حالة حدوث ردود فعل تحسسية مفاجئة وشديدة (على سبيل المثال، ردود فعل تأقية)، يجب إيقاف الحقن على الفور. يجب عليك الاتصال على الفور بطبيبك أو قسم الطوارئ إذا واجهت علامات مبكرة لرد فعل تحسسي، مثل:

·         صعوبة البلع أو التنفس

·         ضيق التنفس أو أزيز

·         الشعور بضيق في الصدر

·         احمرار و/أو تورم الشفاه، أو اللسان، أو الوجه أو اليدين

·         طفح جلدي، أو شري، أو انتبار، أو حكة متفشية

·         شحوب وبرودة في الجلد، وسرعة ضربات القلب، و/أو دوار (انخفاض ضغط الدم)

 

المثبطات (الأجسام المضادة التي تحيد النشاط) حدثت فيما يتعلق بردود الفعل التحسسية الشديدة والمفاجئة (على سبيل المثال، رد فعل تأقي).

لقد لُوحظت الآثار الجانبية التالية مع العلاج بريفكسيا™:

 

الآثار الجانبية الشائعة (ما يصل إلى شخص واحد من كل 10 أشخاص)

·         حكة (هرش)

·         تفاعلات جلدية في موضع الحقن.

 

الآثار الجانبية غير الشائعة (ما يصل إلى شخص واحد من كل 100 أشخاص)

·         ردود الفعل التحسسية (فرط الحساسية).

 

الآثار الجانبية ذات معدل التكرار غير المعروف (وتيرة حدوث هذه الآثار الجانبية غير معروفة)

·         ردود الفعل التأقية

·         تكوين الأجسام المضادة (المثبطات).

 

 

الإبلاغ عن الآثار الجانبية

إذا لاحظت أي آثار جانبية غير موصوفة هنا، ينبغي أن تخبر طبيبك أو الصيدلي.

·         يُحفظ ريفكسيا™ بعيدًا عن رؤية ومتناول الأطفال.

·         لا تستخدم ريفكسيا™ بعد تاريخ انتهاء الصلاحية الموضّح على العلبة الخارجية، والقنينة وملصق المحقنة المُعبأة مُسبقًا بعد كلمة "EXP". يشير التاريخ المطبوع إلى اليوم الأخير من ذلك الشهر.

·         يُخزن في العبوة الأصلية لحماية المحتويات من الضوء.

·         يُحفظ في الثلاجة (من 2-8 درجات مئوية).

·         لا تجمده.

 

قبل تحضير مسحوق ريفكسيا™ للاستخدام، يمكن تخزينه في درجة حرارة الغرفة (حتى 30 درجة مئوية) لمدة لا تزيد عن 6 أشهر. يُرجى ملاحظة التاريخ الذي تبدأ فيه تخزين ريفكسيا™ في درجة حرارة الغرفة، على العلبة الخارجية. لا تقم بإعادة ريفكسيا™ إلى الثلاجة بعد تخزينه بالفعل في درجة حرارة الغرفة.

بمجرد تحضير ريفكسيا™ للاستخدام، ينبغي استخدامه على الفور. وإذا لم تتمكن من استخدام محلول ريفكسيا™ المُحضر على الفور، يمكن تخزين القنينة في درجة حرارة الغرفة (حتى 30 درجة مئوية) لمدة لا تزيد عن 4 ساعات أو في الثلاجة عند درجة حرارة تتراوح بين 2-8 درجات مئوية لمدة لا تزيد عن 24 ساعة. في حالة عدم استخدامه على الفور، قد يصبح الدواء غير معقم وقد يتسبب في حدوث عدوى.

يجب أن يكون المسحوق الموجود في القنينة أبيض أو أصفر قليلًا. لا تستخدم المسحوق إذا كان هناك تغيّر في اللون.

يجب أن يكون المحلول المُعد صافيًا وعديم اللون. لا تستخدم هذا المنتج إذا لاحظت أنه غائم أو يحتوي على جزيئيات مرئية.

لا تتخلص أبدًا من المنتجات الطبية عبر مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من أي دواء لم تعد تستخدمه. فهذه الإجراءات ستساعد على حماية البيئة.

يمكن لطبيبك أو الصيدلي أن يقدم لك مزيدًا من المعلومات بناءً على معلومات الوصف التفصيلية.

 

ما محتويات ريفكسيا™

المادة الفعالة: نوناكوج بيتا بيجول (عامل التخثر البشري التاسع (rDNA)). كما هو محدد بواسطة الشركة المصنّعة، تحتوي كل قنينة من ريفكسيا™ على 500 وحدة دولية، أو 1000 وحدة دولية أو 2000 وحدة دولية من نوناكوج بيتا بيجول.

المكونات الأخرى: كلوريد الصوديوم، سكروز، بولي سوربات 80، هيستيدين، مانيتول، هيدروكسيد الصوديوم و حمض الهيدروكلوريك.

المذيبات: هيستيدين، ماء للحقن، هيدروكسيد الصوديوم وحمض الهيدروكلوريك.

بعد التحضير باستخدام المذيب المتوفر (محلول الهيستيدين)، يحتوي المحلول المُحضر للحقن على 125 وحدة دولية/مل، أو 250 وحدة دولية/مل أو 500 وحدة دولية/مل نوناكوج بيتا بيجول (بناءً على قوة نوناكوج بيتا بيجول، أي 500 وحدة دولية، أو 1000 وحدة دولية، أو 2000 وحدة دولية).

شكل ريفكسيا™ ومحتويات العبوة
يتوفر ريفكسيا™ على شكل مسحوق ومذيب لمحلول الحقن(مسحوق 500 وحدة دولية أو 1000 وحدة دولية أو 2000 وحدة دولية في قنينة و 4 مل مذيب في حقنة معبأة مسبقاً وذراع كبّاس ومهايئ للقنينة - تحتوي العبوة على قنينة واحدة)
• المسحوق لونه أبيض إلى أبيض مائل للصفرة والمذيب صافٍ وعديم اللون.

حامل ترخيص التسويق والشركة المصنّعة

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd، الدنمارك

تاريخ مراجعة النشرة: أغسطس 2017
 Read this leaflet carefully before you start using this product as it contains important information for you

Refixia 500 IU powder and solvent for solution for injection Refixia 1000 IU powder and solvent for solution for injection Refixia 2000 IU powder and solvent for solution for injection

Refixia 500 IU powder and solvent for solution for injection Each vial contains nominally 500 IU nonacog beta pegol*. After reconstitution, 1 ml of Refixia contains approximately 125 IU nonacog beta pegol. Refixia 1000 IU powder and solvent for solution for injection Each vial contains nominally 1000 IU nonacog beta pegol*. After reconstitution, 1 ml of Refixia contains approximately 250 IU nonacog beta pegol. Refixia 2000 IU powder and solvent for solution for injection Each vial contains nominally 2000 IU nonacog beta pegol*. After reconstitution, 1 ml of Refixia contains approximately 500 IU nonacog beta pegol. *recombinant human factor IX, produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology, covalently conjugated to a 40 kDa polyethylene-glycol (PEG). The potency (International Units) is determined using the European Pharmacopeia one-stage clotting test. The specific activity of Refixia is approximately 152 IU/mg protein. Refixia is a purified recombinant human factor IX (rFIX) with a 40 kDa polyethylene-glycol (PEG) selectively attached to specific N-linked glycans in the rFIX activation peptide. Upon activation of Refixia, the activation peptide including the 40 kDa polyethylene-glycol moiety is cleaved off, leaving the native activated factor IX molecule. The primary amino acid sequence of the rFIX in Refixia is identical to the Ala148 allelic form of human plasma-derived factor IX. No additives of human or animal origin are used in the cell culture, purification, conjugation, or formulation of Refixia. Excipient with known effect Less than 1 mmol sodium (23 mg) per vial. For the full list of excipients, see section 6.1.

Powder and solvent for solution for injection. The powder is white to off-white. The solvent is clear and colourless. pH: 6.4. Osmolality: 272 mOsmol/kg.

Treatment and prophylaxis of bleeding in previously treated patients with hemophilia B (congenital factor IX deficiency).


Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.

Previously untreated patients

The safety and efficacy of Refixia® in previously untreated patients has not been examined. Limited data are currently available.

 

Treatment monitoring

Routine monitoring of factor IX activity levels with the goal of dose adjustment is generally not required. No dose adjustment was made in the clinical trial program. Mean trough levels of factor IX steady state above 15% were observed in all age groups, see section 5.2 for details.

 

For modified long-acting factor preparations, the results of the one-step coagulation test are known to be highly dependent on the aPTT reagents used and the reference standard. For Refixia®, polyethylene glycol (PEG) may cause interference in the one-step coagulation test, but not in the chromogenic test. Certain aPTT reagents such as Cephascreen® and SynthaFax® have been proven in laboratory studies to be worthwhile for reliable monitoring after the infusion of Refixia®. However, it is recommended that silicon based reagents not be used as they may result in overestimates. The chromogenic test is not affected by PEG and the FIX kits ROX FACTOR IX and BIOPHEN Factor IX have in laboratory studies proven their worth for use with nonacog beta pegol. They can be used for reliable monitoring after the administration of Refixia®.

 

Posology

One International Unit (IU) of factor IX activity is equivalent to the amount of factor IX in a milliliter of normal human plasma.

 

Prophylaxis

Subjects who are treated for long-term prophylaxis and miss a dose will be instructed to administer their dose when they forget to do so and then continue with their usual dosing schedule of a weekly dose. A double dose should be avoided. The recommended dose for the prophylaxis of bleeding in adult previously treated patients with hemophilia B (congenital factor IX deficiency) is 40 IU/kg of Refixia®.

 

On-demand treatment

Dose and duration of the substitution therapy depend on the location and severity of the bleeding, see Table 1 for dosing guidance in bleeding episodes.

 

Table 1       Treatment of bleeding episodes with Refixia

Degree of severity of bleeding

Recommended dose IU/kg of Refixia®

Dosing recommendations

Hemarthrosis at an early stage, muscle bleeding or bleeding in the oral cavity

Advanced hemarthrosis, muscle bleeding, or hematomas

40

A single dose is recommended.

Severe or life-threatening bleeding.

80

Additional doses of 40 IU/kg may be administered..

 

Surgery

The dose level and dosing intervals for surgery depend on the procedure and local practice. Refer to Table 2 for general recommendations.

 

Table 2       Treatment in surgery with Refixia®

Type of surgery

Recommended dose IU/kg body weight

Dosing recommendations

Minor operations, including the extraction of teeth

40

Additional doses may be administered as needed.

Major surgery.

80

Pre-operative dose.

40

Consider two repeated doses of 40 IU/kg (at intervals of 1-3 days) within the first week after surgery.

 

Due to the long half-life of Refixia®, the product can be administered once a week after the first week of the postoperative period until bleeding stops and healing is achieved.

 

Paediatric population

 In children, the same dose is recommended as in adults: 40 IU/kg of body weight.

Method of administration Intravenous use.

 

Refixia® is administered by intravenous bolus injection over several minutes after reconstitution of the powder for injection with the histidine solvent. The rate of administration should be determined by the patient’s comfort level up to a maximum injection rate of 4 ml/min.

 

For instructions on how to reconstitute the medicinal product prior to administration, see section 6.6.

 

Appropriate training is recommended prior to administration of the product.

 

In order to ensure the traceability of biotechnologically manufactured medicinal products, it is recommended that the trade name and batch number be documented in the case of each treatment.


Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Known allergic reaction to hamster protein.

Hypersensitivity

As with all protein products for intravenous use, hypersensitivity reactions typical of allergy are also possible with Refixia®. The preparation contains trace amounts of hamster proteins. Patients should be advised to discontinue the use of the medicinal product immediately in the event of signs of hypersensitivity and to contact the treating physician. You must be informed of the first signs of hypersensitivity reactions, including hives, generalized urticaria, chest tightness, wheezing, low blood pressure and anaphylaxis.

 

In case of anaphylactic shock, current medical standards of shock treatment should be followed.

Inhibitors

After repeated treatment with human coagulation factor IX (rDNA) products, patients should be

monitored for the development of neutralising antibodies (inhibitors) that should be quantified in Bethesda Units (BU) using appropriate biological testing.

 

There have been reports in the literature showing a correlation between the occurrence of a factor IX inhibitor and allergic reactions. Therefore, patients experiencing allergic reactions should be evaluated for the presence of an inhibitor. It should be noted that patients with factor IX inhibitors may be at an increased risk of anaphylaxis with subsequent challenge with factor IX.

 

Due to the risk of allergic reactions that may occur with factor IX preparations, the first administration of factor IX should be performed under medical supervision according to the treating physician’s judgment so that appropriate medical care can be provided in case of allergic reactions.

 

Thromboembolism

Due to the potential risk of thrombotic complications, clinical monitoring for early signs of thrombotic and consumption coagulopathy should be initiated by appropriate biological testing when administered to patients with liver disease, postoperative patients, neonates, or patients at risk of thrombotic phenomena or DIC. In these situations, the benefits of treatment with Refixia® must be balanced against the risk of these complications.

 

Immunological tolerance induction

The safety and efficacy of the use of Refixia® for immunological tolerance induction have not been studied.

 

Nephrotic syndrome

Nephrotic syndrome has been reported following attempted treatment for immunological tolerance induction with factor IX in patients with hemophilia B and often a history of allergic reaction.

 

 

Catheter-related complications

If a central venous access device (CVAD) is required, the risk of CVAD-associated complications, including local infection, bacteremia, and thrombosis at the catheter insertion site, should be considered.

 

Paediatric population

The listed warnings and precautions apply to both adults and children.


No interactions of human coagulation factor IX (rDNA) preparations with other medicinal products have been reported.


Animal reproductive studies have not been conducted with factor IX. Due to the rare occurrence of hemophilia B in women, there is no clinical experience with the use of factor IX during pregnancy and breastfeeding. Therefore, factor IX should only be used during pregnancy and lactation if clearly indicated.


Refixia® has no influence on the ability to drive and use machines.


Summary of the safety profile

Hypersensitivity or allergic reactions (including angioedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed rarely with recombinant factor IX products and may in some cases progress to severe anaphylaxis (including shock). In some cases, these reactions have developed to severe anaphylaxis, and have  occurred in close temporal association with development of factor IX inhibitors (see also section 4.4). Nephrotic syndrome has been reported following attempted immunological tolerance induction with factor IX inhibitors in patients with hemophilia B and a history of allergic reaction.

 

Very rarely development of antibodies to hamster protein with related hypersensitivity reactions has been observed.

 

Patients with hemophilia B may develop neutralizing antibodies (inhibitors) to factor IX. The occurrence of such inhibitors manifests as an inadequate clinical response. In such cases, contact with a specialized hemophilia center is recommended.

 

There is a potential risk of thromboembolic episodes following the administration of factor IX preparations, with a higher risk for low purity preparations. The use of low purity factor IX preparations has been associated with cases of myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism. The use of high purity factor IX such as Refixia® is rarely associated with such adverse effects.

 

Tabulated list of adverse reactions

The table below is based on MedDRA Organ Classes (SOC and Preferred Term Level).

 

Frequencies are defined as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

 

Within each frequency class, adverse reactions are listed in order of decreasing severity.

 

Previously treated patients:

A total of 115 previously treated male patients with moderate or severe hemophilia B received Refixia® for a total of 170 patient-years in the clinical trials conducted.

 

Table 3       Frequency of adverse reactions in clinical trials

System Organ Class

Frequency (%)

Adverse effect

Immune system disorders

0.9 (1/115, uncommon)

Hypersensitivity

Skin and subcutaneous tissue disorders

2.6 (3/115, common)

Pruritus**

General disorders and application site reactions

3.5 (4/115, common)

Reactions at the injection site***

*Number of patients with reaction divided by the sum of all patients exposed in all clinical trials (115).

**Pruritus includes the terms pruritus and ear itching

***Injection site reactions include injection site pain, infusion site pain, injection site swelling, injection site erythema and  injection site rash.

 

Previously untreated patients

In an ongoing trial in previously untreated patients, anaphylaxis has occurred in close temporal association with development of factor IX inhibitors after treatment with Refixia®. The likelihood of developing the inhibitor and an anaphylactic reaction is increased in the early phases of substitution treatment (see section 4.4).

 

Description of selected adverse effects

Not applicable

 

Peadiatric population

Previously treated patients: No differences in the safety profile of Refixia® were observed between previously treated children and adults.

 

Previously untreated patients: See undesirable effects under “Tabular presentation of undesirable effects” – “Undesirable effects in previously untreated patients”.

 

Reporting of suspected adverse reactions

The National Pharmacovigilance and Drug Safety Centre (NPC):

o Fax: +966-11-205-7662

o  SFDA call centre 19999

o  Toll free phone: 8002490000

o  E-mail: npc.drug@sfda.gov.sa

o  Website: www.sfda.gov.sa/npc


 Overdoses up to 169 IU/kg have been reported in clinical trials. No symptoms associated with overdoses have been reported.


Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor IX, ATC code: B02BD04.

Mechanism of action

Refixia® is a purified recombinant human factor IX (rFIX) conjugated with a 40 kDa polyethylene glycol (PEG). The mean molecular mass of Refixia® is approximately 98 kDa and the molecular mass of the protein content alone is 56 kDa.

 

Factor IX is a single-chain glycoprotein. It is a vitamin K-dependent coagulation factor that is synthesized in the liver. Factor IX is activated by factor XIa and factor VII/tissue factor complex.

 

After the activation of Refixia®, the activation peptide, including the 40 kDa polyethylene glycol molecule, is cleaved, leaving the original factor IX molecule. Activated factor IX, in combination with activated factor VIII, activates factor X. Activated factor X converts prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin, creating a clot.

 

Hemophilia B is a sex-linked hereditary clotting disorder in which the decreased levels of factor IX result in severe bleeding into joints, muscles, or internal organs either spontaneously or as a result of an accident or surgical trauma. Factor IX plasma levels are increased by substitution treatment, with temporary correction of factor deficiency and bleeding diathesis.

 

Clinical efficacy

The clinical trial program conducted included a Phase 1 study and four multicenter, uncontrolled Phase 3 studies. The total number of previously treated male patients with hemophilia B (factor IX activity ≤2%) included in the clinical trial program was 115; 72 adult patients (aged 18 years and older), 18 adolescents (aged 13 to 17 years) and 25 children (aged 0 to 12 years). Ten patients participated in only the single-dose PK study. The overall exposure in the clinical trial program was 8,801 days of exposure with Refixia® and 40 (35%) of the 115 patients were treated for more than 2 years. Of these patients, 21 children continued treatment in the extension phase of the ongoing pediatric study with at least 2 years of treatment.

 

The pivotal study included 74 previously treated adolescents (13 to 17 years) and adults (18 to 65 years). The study included an open-label arm in which patients were treated as needed and were treated for approximately 28 weeks, and two prophylaxis arms with single-blind randomization at 10 IU/kg or 40 IU/kg once weekly for approximately 52 weeks. Only the prophylactic dose of 40 IU/kg resulted in a pre-defined reduction in the annualized bleeding rate compared to the clinically relevant annualized bleeding rate from the history. When comparing the 10 IU/kg and 40 IU/kg treatments, the annualized bleeding rate of patients in the 40 IU/kg arm was 49% lower than the bleeding rate of patients in the 10 IU/kg arm (p < 0.05).

 

The treatment period in the pediatric study included 52 weeks. Included in the studies were 25 previously treated pediatric patients (aged 0 to 12 years) who received a prophylactic dose of 40 IU/kg once a week.

 

In the studies, bleeding episodes were treated with Refixia® 40 IU/kg for mild or moderate bleeding or 80 IU/kg for severe bleeding.

 

An overall assessment of efficacy was made by the patient (treatment at home) or the investigator at the study site (treatment under the supervision of healthcare professionals) using a 4-point scale (excellent, good, moderate, or poor). The overall success rate (defined as excellent or good) for the treatment of bleeding was 93% (551 of 591) after pooling all studies. Of 597 bleeds treated, which occurred in 79 (75%) of the 105 patients, 521 (87%) were stopped with one injection and another 60 (10%) with 2 injections of Refixia®.

 

The success rate and dose required to treat bleeding episodes were independent of the location of the bleeding. The success rate of the treatment of bleeding episodes was also not dependent on whether the bleeding was traumatic or spontaneous in nature.

 

 

Prophylaxis

54 (47%) of patients were treated with a weekly prophylactic dose of 40 IU/kg. No bleeding episodes occurred in 23 (43%) of these patients. The median annualized bleeding rates for these patients are presented in Table 4.

 

Table 4       Annualized bleeding rates in patients (0-65 years) treated with a prophylactic dose of 40 IU/kg once weekly (median (IQR))

 

 

                                       Previously treated patients (factor IX<2%)

 

 

0-6

years

N=12

7-12

years

N=13

13 to 17

years

N=9

18 to 65

years

N=20

0 to 65

years

N=54

Annualized

spontaneous

bleeding rate

0.00

(0.00; 0.00)

0.00

(0.00; 0.68)

0.00

(0.00; 0.00)

0.00

(0.00;

1.51)

0.00

(0.00;

0.80)

Annualized

traumatic

bleeding rate

0.00

(0.00; 1.48)

0.00

(0.00; 1.93)

1.93

(0.00; 3.87)

0.00

(0.00;

1.01)

 

0.00

(0.00;

1.96)

 

Annualized

joint bleeding

rate

0.00

(0.00; 0.00)

 

0.68

(0.00; 1.63)

0.97

(0.00; 2.17)

0.51

(0.00;

2.04)

 

0.00

(0.00;

1.97)

 

Total

annualized

bleeding rate

0.00

(0.00; 1.78)

2.00

(0.68; 2.89)

1.93

(0.00; 4.01)

 

1.03

(0.00;

4.01)

 

1.03

(0.00;

2.89]

 

 

In the pivotal adolescent and adult study, all patients who experienced spontaneous bleeding during the period of once-weekly prophylaxis with nonacog beta pegol 40 IU/kg also had pre-existing joint disease in one or more joints at baseline as a result of their hemophilia B.

 

Out of 29 treated adults and adolescents, 13 patients with 20 target joints received a weekly prophylactic dose of 40 IU/kg for one year. 18 of these 20 joints (90%) were no longer considered target joints at the end of the study.

 

Acute treatment

The pivotal study included a non-randomized arm in which 15 patients received acute treatment with 40 IU/kg for mild and moderate bleeding and 80 IU/kg for major bleeding. The overall success rate (defined as excellent or good) for the treatment of bleeding was 95%, with 98% of bleeding treated with one injection or two injections.

 

Paediatric population

The European Medicines Agency has postponed the conduct of the study with Refixia® in previously untreated patients (see section “Posology/Administration” for information on use in children).

 

 

Surgery

Three studies, of which this was a dedicated surgical study, included a total of 15 more major and 26 more minor surgical procedures (patients aged 13 to 56 years). The hemostatic effect of Refixia® during surgery was confirmed with a success rate of 100% in the 15 more major surgical procedures in the studies. All more minor surgeries assessed were successfully performed.

 

In a dedicated surgery study, the efficacy analysis included 13 more major surgeries performed in 13 previously treated adults and adolescents. These were 9 orthopedic surgeries, 1 gastrointestinal surgery and 3 surgeries in the oral cavity. Patients received a preoperative injection of 80 IU/kg on the day of surgery and post-operative injections of 40 IU/kg.

 

A preoperative dose of 80 IU/kg of Refixia® was effective and no patient required additional doses on the day of surgery. In the postoperative period Days 1 to 6 and Days 7 to 13, the median number of additional 40 IU/kg doses was 2.0 and 1.5, respectively. The mean total consumption of Refixia® during and after surgery was 241 IU/kg (range: 81 to 460 IU/kg).


Refixia® has an extended half-life compared to unmodified factor IX. All pharmacokinetic studies of Refixia® were conducted in previously treated patients with hemophilia B (factor IX ≤2%). Plasma samples were analyzed using the one-stage coagulation test.

 

Steady-state pharmacokinetic parameters for adolescents and adults are shown in Table 5.

 

Table 5       Steady state pharmacokinetic parameters of Refixia (40 IU/kg) in adolescents and adults (geometric mean (CV%))

PK Parameter

13–17 years N=3

≥18 years N=6

Half-life (t1/2) (hours)

103 (14)

115 (10)

Incremental Recovery (IR) (IU/ml per IU/kg)

0.018 (28)

0.019 (20)

Area under the curve (AUC)0-168h (IU*hours/ml)

91 (22)

93 (15)

Clearance (CL) (ml/hour/kg)

0.4 (17)

0.4 (11)

Mean residence time (MRT) (hours)

144 (15)

158 (10)

Volume of distribution (Vss) (ml/kg)

61 (31)

66 (12)

Factor IX activity 168 h post dosing (IU/ml)

0.29 (19)

0.32 (17)

Clearance = body weight adjusted clearance; Incremental recovery = incremental recovery 30 min post dosing, Volume of

distribution = body weight adjusted volume of distribution at steady state. CV = coefficient of variation.

 

In all patients evaluated in the steady-state PK study, activity levels were above 0.24 IU/mL with weekly administration of 40 IU/kg of factor IX 168 hours post dose.

 

The pharmacokinetic parameters of a single dose of Refixia® in children, adolescents and adults are presented by age in Table 6.

 

 

Table 6       Pharmacokinetic parameters of a single dose of Refixia® (40 IU/kg) in children, adolescents and adults by age (geometric mean (CV))

PK Parameter

0–6 years N=12

7–12 years N=13

13–17 years N=3

≥18 years N=6

Half-life (t1/2) (hours)

70 (16)

76 (26)

89 (24)

83 (23)

Incremental Recovery (IR) (IU/ml per IU/kg)

0.015 (7)

0.016 (16)

0.020 (15)

0.023 (11)

Area under the curve (AUC)inf (IU*hours/ml)

46 (14)

56 (19)

80 (35)

91 (16)

Clearance CL (ml/hour/kg)

0.8 (13)

0.6 (22)

0.5 (30)

0.4 (15)

Mean residence time (MRT) (hours)

95 (15)

105 (24)

124 (24)

116 (22)

Volume of distribution (Vss) (ml/kg)

72 (15)

68 (22)

59 (8)

47 (16)

Factor IX activity 168 h post dosing (IU/ml)

0.08 (16)

0.11 (19)

0.15 (60)

0.17 (31)

Clearance = body weight adjusted clearance; Incremental recovery = incremental recovery 30 min post dosing, Volume of distribution = body weight adjusted volume of distribution at steady state. CV = coefficient of variation.

 

As expected, body weight adjusted clearance in paediatric and adolescent patients was higher compared to adults. No dose adjustment was necessary for paediatric or adolescent patients.

 

The estimated mean steady-state trough levels found during studies with weekly administration of 40 IU/kg are shown in Table 7.

 

Table 7       Refixia® factor IX trough levels* (40 IU/kg) by age at steady state

 

0–6 years

7–12 years

13–17 years

18–65 years

 

N=12

N=13

N=9

N=20

Estimated mean

factor IX trough

levels IU/ml

(95% CI)

0.15

(0.13;0.18)

0.19

(0.16;0.22)

0.24

(0.20;0.28)

0.29

(0.26;0.33)

* Factor IX trough level = factor IX activity measured at all visits prior to the following weekly dose (5 to 10 days post dose).

 

Pharmacokinetics were investigated in 16 adult and adolescent patients of which 6 were normal weight (BMI 18.5–24.9 kg/m2) and 10 were overweight (BMI 25–29.9 kg/m2). There were no apparent differences in the pharmacokinetic profiles between normal weight and overweight patients.

 

Steady-state factor IX activity profiles were simulated using a onec-ompartment distribution model with first-order elimination kinetics with PK parameters for clearance (CL) and volume of distribution (Vss) at steady state.

Patients with hemophilia B (older than 13 years) treated with 40 IU/kg Refixia® once weekly have predicted factor IX activity above 0.40 IU/mL for 130 out of 168 hours, corresponding to 80% of the week.

 

Pharmacokinetics were assessed in 16 adults and adolescents, with 6 patients being of normal weight (BMI 18.5-24.9 kg/m2) and 10 being overweight (BMI 25-< 29.9 kg/m2). There were no apparent differences in the pharmacokinetic profiles of normal and overweight patients. Pharmacokinetic parameters were not affected by BMI.


The preclinical data based on the usual studies on safety, pharmacology and repeated-dose toxicity in animals do not indicate any concerns in the case of humans.

 

Long-term studies in animals that are intended to determine the carcinogenic potential of Refixia® and studies to determine the effects of Refixia® on genotoxicity, fertility, development or reproduction have not been conducted.

 

A review of the carcinogenic potential of Refixia® was conducted, with no carcinogenic risk identified.


Powder

Sodium chloride

Histidine

Sucrose

Polysorbate 80

Mannitol

Sodium hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)

 

Solvent

Histidine

Water for injections

Sodium hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)


In the absence of compatibility studies, Refixia® must not be mixed or reconstituted with solvents other than the accompanying histidine solution.

 

Do not administer reconstituted Refixia® through the same tubing and containers as other medicinal products.


Unopened 24 months at 2°C-8°C, while Refixia® can be stored at room temperature (not above 30°C) for no more than 6 months. Once the product is removed from the refrigerator, it should not be put back into the refrigerator. Please note the start of storage at room temperature on the package. After reconstitution The reconstituted preparation should be used up immediately. Chemical and physical stability during use has been demonstrated with 24-hour refrigeration (2°C-8°C) and 4-hour room temperature storage (≤30°C). If the product is not used immediately, the duration and conditions of storage prior to use are the responsibility of the user. It is generally not recommended to use preparations stored at room temperature (≤30°C) for more than 4 hours or refrigerated for 24 hours (2°C-8°C) unless reconstitution has been performed under controlled and validated aseptic conditions. Any unused product stored at room temperature for more than 4 hours should be discarded. Refixia® should only be used until the date stated on the package labeled “EXP”.

Store in a refrigerator (2°C – 8°C). Do not freeze.

Store in the original package in order to protect from light.

Keep out of the sight and reach of children.

For storage at room temperature and storage conditions after reconstitution of the medicinal product, see section 6.3.


Each pack contains:

–               1 glass vial (type I) with powder and chlorobutyl rubber stopper

–               1 sterile vial adapter for reconstitution

–               1 pre-filled syringe of 4 ml histidine solvent with backstop (polypropylene), a rubber plunger (bromobutyl) and a tip cap with a stopper (bromobutyl)

–               1 plunger rod (polypropylene).

Pack size of 1.


Refixia® should be administered intravenously after reconstitution of the

powder with the solvent provided in the injection syringe. After reconstitution, the solution appears to be a clear and colorless solution that is free of visible particles. The reconstituted medicinal product should be visually inspected for particulate matter and discoloration prior to administration. Do not use solutions that are cloudy or have deposits.

The rate of administration should depend on the patient’s condition, with a maximum injection rate of 4 mL/min.

You will also need an infusion set (tubing and butterfly needle), sterile alcohol wipes, gauze pads, and patches. These materials are not included with Refixia®.

Always use an aseptic technique.

Disposal

Dispose of the syringe containing the infusion set and vial with the adapter for the vial safely after injection. Dispose of any unused product and other waste materials according to local requirements.


Novo Nordisk A/S Novo Allé DK-2880 Bagsværd Denmark

Date of revision: August 2017
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