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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)

Vizimpro contains the active substance dacomitinib, which belongs to a group of medicines called protein tyrosine kinase inhibitors which are used to treat cancer.

 

Vizimpro is used to treat adults with a type of lung cancer called ‘non-small cell lung cancer’. If a test has shown that your cancer has certain changes (mutations) in a gene called ‘EGFR’ (epidermal growth factor receptor) and has spread to your other lung or other organs, your cancer is likely to respond to treatment with Vizimpro.

 

Vizimpro can be used as your first treatment once your lung cancer has spread to your other lung or other organs.


Do not take Vizimpro

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

 

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Vizimpro:

  • if you ever had any other lung problems. Some lung problems may get worse during treatment with Vizimpro, as Vizimpro may cause inflammation of the lungs during treatment. Symptoms may be similar to those from lung cancer. Tell your doctor right away if you have any new or worsening symptoms including difficulty in breathing, shortness of breath, or cough with or without phlegm (mucous), or fever.
  • If you are being treated with any of the medicines listed in section Other medicines and Vizimpro.

 

Tell your doctor immediately while taking this medicine:

  • if you develop diarrhoea. Immediate treatment of diarrhoea is important.
  • if you develop skin rash. Early treatment of skin rash is important.
  • if you have any symptoms of a liver problem which may include: yellowing of your skin or the white part of your eyes (jaundice), dark or brown (tea coloured) urine, light-coloured bowel movements (stools).

 

Children and adolescents

Vizimpro has not been studied in children or adolescents and it must not be given to patients under the age of 18 years.

 

Other medicines and Vizimpro

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

 

In particular, the effects of some medicines may increase when taken with Vizimpro. These include, among others:

  • Procainamide, used to treat heart arrhythmias
  • Pimozide and thioridazine, used to treat schizophrenia and psychosis

 

You should not take these medicines during your treatment with Vizimpro.

 

The following medicines may reduce how well Vizimpro works:

  • Long-acting medicines for reducing stomach acid, such as proton pump inhibitors (for ulcers, indigestion and heartburn).

 

You should not take these medicines during your treatment with Vizimpro. As an alternative, you can take a short‑acting medicine, such as an antacid, or an H2 blocker medicine. If you take H2 blocker medicine take your dose of Vizimpro at least 2 hours before or 10 hours after taking the H2 blocker medicine.

 

The following medicine may increase how well Vizimpro works:

  • Paroxetine (for depression, anxiety disorders, or obsessive-compulsive disorder (OCD)).

 

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

 

Pregnancy

You should not become pregnant during treatment with Vizimpro because this medicine could harm the baby. If there is any possibility that you may become pregnant you must use effective contraception during treatment, and for at least 17 days afterwards. If you become pregnant while taking this medicine, you should immediately talk to your doctor.

 

Breast-feeding

Do not breast-feed while taking this medicine because it is not known if it can harm your baby.

 

Driving and using machines

Tiredness and eye irritation can occur in patients taking Vizimpro. If you feel tired or your eyes are irritated, you should use caution when driving or using machines.

                                                                                                         

Vizimpro contains lactose and sodium

This medicine contains lactose (found in milk or dairy products). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

 

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium‑free”.


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

 

  • The recommended dose is 45 mg taken by mouth each day.
  • Take the tablet at about the same time each day.
  • Swallow the tablet whole with a glass of water.
  • You can take the tablet with or without meals.

 

Your doctor may decrease the dose of your medicine depending on how well you tolerate it.

 

If you take more Vizimpro than you should

If you have taken too much Vizimpro, see a doctor or go to a hospital immediately.

 

If you forget to take Vizimpro

If you miss a dose or vomit, take your next dose as scheduled. Do not take a double dose to make up for a forgotten tablet.

 

If you stop taking Vizimpro

Do not stop taking Vizimpro unless your doctor tells you to. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

 


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

 

Contact your doctor immediately if you notice any of the following side effects – you may need urgent medical treatment:

·   Inflammation of the lungs (common, may affect up to 1 in 10 people)

Difficulty in breathing, shortness of breath, possibly with a cough or fever. This may mean that you have an inflammation of the lungs called interstitial lung disease and can be fatal.

·   Diarrhoea (very common, may affect more than 1 in 10 people)

Diarrhoea may lead to fluid loss (common), low blood potassium (very common), and worsening kidney function and can be fatal. At first signs of increased frequency of bowel movements, contact your doctor immediately, drink plenty of fluids, and start antidiarrhoea treatment as soon as possible. You should have an anti‑diarrhoeal medicine available before you start taking Vizimpro.

·   Skin rash (very common)

It is important to treat the rash early. Tell your doctor if a rash starts. If treatment for rash is not working or the rash is getting worse (for example, you have peeling or cracking of the skin) you should tell your doctor immediately, since your doctor may decide to stop your treatment with Vizimpro. Rash may occur or worsen in areas exposed to sun. Sun protection with protective clothing and sunscreen is recommended.

 

Tell your doctor as soon as possible if you notice any of the other following side effects:

 

Very common (may affect more than 1 in 10 people):

·   Inflammation of the mouth and lips

·   Nail problems

·   Dry skin

·   Loss of appetite

·   Dry, red, or itchy eyes

·   Weight loss

·   Hair loss

·   Itching

·   Abnormal liver enzyme blood tests

·   Nausea or vomiting

·   Flushed or painful palms or soles

·   Tiredness

·   Weakness

·   Cracks in the skin

 

Common (may affect up to 1 in 10 people):

·   Alteration in taste

·   Peeling skin

·   Eyes inflammation

·   Abnormal amount of body hair growth

 

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the National Pharmacovigilance Centre (NPC). By reporting side effects you can help provide more information on the safety of this medicine.

 

To report any side effect(s):

 

Saudi Arabia:

 

National Pharmacovigilance Centre (NPC)

·       Call center: 19999

·       E-mail: npc.drug@sfda.gov.sa

·       Website: https://ade.sfda.gov.sa/

 

 Other GCC States:

 

 Please contact the relevant competent authoity


Store below 30°C.

 

After opening store below 30°C and use it within 100 days

 

Keep this medicine out of the sight and reach of children.

 

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

 

 

This medicine may pose a risk for the environment. 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 dacomitinib (as dacomitinib monohydrate). Vizimpro film-coated tablets come in different strengths.

Vizimpro 15 mg tablet: each film-coated tablet contains 15 mg dacomitinib

Vizimpro 30 mg tablet: each film-coated tablet contains 30 mg dacomitinib

Vizimpro 45 mg tablet: each film-coated tablet contains 45 mg dacomitinib

-                 The other ingredients are:

Tablet core: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, magnesium stearate (see section 2 Vizimpro contains lactose and sodium).

Film coating: Opadry II Blue 85F30716 containing polyvinyl alcohol – partially hydrolysed (E1203), talc (E553b), titanium dioxide (E171), macrogol (E1521), Indigo carmine aluminium lake (E132).


- Vizimpro 15 mg film-coated tablets are supplied as blue film-coated, round biconvex tablets, debossed with “Pfizer” on one side and “DCB15” on the other. - Vizimpro 30 mg film-coated tablets are supplied as blue film-coated, round biconvex tablet, debossed with “Pfizer” on one side and “DCB30” on the other. - Vizimpro 45 mg film-coated tablets are supplied as blue film-coated, round biconvex tablet, debossed with “Pfizer” on one side and “DCB45” on the other. It is available in bottles packs of 30 film-coated tablets (tablets).

Marketing Authorisation Holder

Pfizer Inc.

66 Hudson Boulevard East, NY 10001,

New York, United Sates of America

 

Manufacturer

Pfizer Manufacturing Deutschland GmbH

Betriebsstatte, Freiburg,

Germany


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

يحتوي فيزيمبرو على المادة الفعالة داكوميتينيب التي تنتمي إلى مجموعة من الأدوية تسمى مثبطات بروتين كيناز التيروزين المستخدمة لعلاج السرطان.

 

يُستخدم فيزيمبرو لعلاج البالغين المصابين بنوع من سرطان الرئة يُسمى "سرطان الرئة ذو الخلايا غير الصغيرة". إذا أظهر أحد الاختبارات أن السرطان الذي تعاني منه به تغيرات معينة (طفرات) في جين يُسمى "EGFR" (مستقبل عامل النمو البشروي) وأنه قد انتشر إلى رئتك الأخرى أو إلى أعضاء أخرى، فمن المرجح أن يستجيب السرطان الذي تعاني منه للعلاج بفيزيمبرو.

 

يمكن استخدام فيزيمبرو كعلاج أول لك بمجرد انتشار سرطان الرئة الذي تعاني منه إلى رئتك الأخرى أو إلى أعضاء أخرى.

 

موانع استعمال فيزيمبرو:

  • إذا كنت مصابًا بالحساسية تجاه داكوميتينيب أو أي من المكونات الأخرى لهذا الدواء (المدرجة في القسم ٦).

 

الاحتياطات عند استعمال فيزيمبرو

تحدث مع طبيبك أو الصيدلي أو الممرضة قبل تناول فيزيمبرو:

  • إذا كنت قد عانيت من قبل من أي مشكلات أخرى بالرئة. قد تتفاقم بعض مشكلات الرئة أثناء العلاج بفيزيمبرو، لأن فيزيمبرو قد يتسبب في التهاب الرئتين أثناء العلاج. قد تكون الأعراض مشابهة لأعراض سرطان الرئة. أخبر طبيبك على الفور إذا أصبت بأي أعراض جديدة أو إذا تفاقمت أعراضك، بما في ذلك صعوبة التنفس، أو ضيق التنفس، أو السعال المصحوب أو غير المصحوب بالبلغم (المخاط)، أو الحمى.
  • إذا كنت تخضع للعلاج بأي من الأدوية المدرجة في قسم "الأدوية الأخرى وفيزيمبرو".

 

أخبر طبيبك على الفور خلال تناول هذا الدواء:

  • إذا أصبت بالإسهال. العلاج الفوري للإسهال مهم.
  • إذا أصبت بطفح جلدي. العلاج المبكر للطفح الجلدي مهم.
  • إذا أصبت بأي أعراض لمشكلات الكبد التي قد تتضمن: اصفرار جلدك أو الجزء الأبيض من عينيك (اليرقان)، تغير لون البول إلى لون داكن أو بني (لون الشاي)، تغير لون الغائط (البراز) إلى لون فاتح.

 

الأطفال والمراهقون

لم تتم دراسة استخدام فيزيمبرو مع الأطفال أو المراهقين ويجب ألا يُعطى للمرضى الذين تقل أعمارهم عن ١٨ عامًا.

 

التداخلات الدوائية مع أخذ هذا المستحضر مع أي أدوية أخرى أو أعشاب أو مكملات غذائية

أخبر طبيبك أو الصيدلي إذا كنت تتناول، أو تناولت مؤخرًا، أو قد تتناول أي أدوية أخرى.

 

على وجه الخصوص، قد تزداد آثار بعض الأدوية عند تناولها مع فيزيمبرو. تتضمن هذه الأدوية، من بين أدوية أخرى:

  • بروكايناميد، يستخدم لعلاج اضطراب ضربات القلب
  • بيموزيد وثيوريدازين، يستخدمان لعلاج الفصام والذهان

 

ينبغي ألا تتناول هذه الأدوية أثناء علاجك بفيزيمبرو.

 

قد تقلل الأدوية التالية من كفاءة عمل فيزيمبرو:

  • الأدوية طويلة المفعول المستخدمة لتقليل حمض المعدة، مثل مثبطات مضخة البروتون (لعلاج القرح، وعسر الهضم، وحرقة فم المعدة).

 

ينبغي ألا تتناول هذه الأدوية أثناء علاجك بفيزيمبرو. وكبديل لهذا، يمكنك تناول دواء قصير المفعول، مثل مضاد للحموضة، أو دواء حاصر لمستقبلات الهيستامين ٢. إذا تناولت دواءً حاصرًا لمستقبلات الهيستامين ٢، فتناول جرعتك من فيزيمبرو قبل ساعتين على الأقل من تناول الدواء الحاصر لمستقبلات الهيستامين ٢ أو بعد تناوله بـ١٠ ساعات على الأقل.

 

إن الدواء التالي قد يزيد من فعالية فيزيمبرو:

·         باروكستين (للاكتئاب، أو اضطرابات التوتر، أو اضطراب الوسواس القهري (OCD)).

 

الحمل والرضاعة

إذا كنتِ حاملًا، أو تُرضعين رضاعة طبيعية، أو تعتقدين أنكِ ربما تكونين حاملًا، أو تخططين للإنجاب، فاستشيري طبيبكِ أو الصيدلي قبل تناول هذا الدواء.

 

الحمل

ينبغي ألا تصبحي حاملًا أثناء العلاج بفيزيمبرو لأن هذا الدواء قد يسبب ضررًا للطفل. إذا كان هناك أي احتمال أنكِ قد تصبحين حاملًا، يجب أن تستخدمي وسيلة فعالة لمنع الحمل أثناء العلاج ولمدة ١٧ يومًا على الأقل بعد ذلك. إذا أصبحتِ حاملًا أثناء تناول هذا الدواء، ينبغي أن تتحدثي إلى طبيبكِ على الفور.

 

الرضاعة الطبيعية

لا ترضعي طفلكِ رضاعة طبيعية أثناء تناول هذا الدواء لأنه من غير المعروف ما إذا كان من الممكن أن يسبب ضررًا لطفلكِ أم لا.

 

تأثير فيزيمبرو على القيادة واستخدام الآلات

قد يحدث تعب وتهيج بالعين لدى المرضى الذين يتناولون فيزيمبرو. إذا شعرت بتعب أو تهيج في عينيك، ينبغي أن تتوخى الحذر عند القيادة أو استخدام الآلات.

 

معلومات هامة حول بعض مكونات فيزيمبرو

يحتوي فيزيمبرو على لاكتوز وصوديوم

يحتوي هذا الدواء على لاكتوز (يوجد في الحليب أو منتجات الألبان). إذا كان طبيبك قد أخبرك أنك لا تستطيع تحمل بعض السكريات، فتواصل معه قبل تناول هذا الدواء.

 

يحتوي هذا الدواء على أقل من ١ مليمول من الصوديوم (٢٣ ملجم) لكل قرص؛ أي أنه "خال من الصوديوم" بشكل أساسي.

 

https://localhost:44358/Dashboard

احرص دومًا على تناول هذا الدواء بالضبط كما أخبرك طبيبك أو الصيدلي. راجع طبيبك أو الصيدلي إذا لم تكن متأكدًا مما ينبغي فعله.

 

  • الجرعة الموصى بها هي 45 ملجم تؤخذ عن طريق الفم كل يوم.
  • تناول القرص في الوقت نفسه تقريبًا كل يوم.
  • ابتلع القرص كاملًا مع كوب من الماء.
  • يمكنك تناول الأقراص مع الوجبات أو من دونها.

 

قد يقلل طبيبك جرعة دوائك وفقًا لدرجة تحملك له.

 

إذا تناولت كمية أكبر مما ينبغي من فيزيمبرو

إذا تناولت كمية أكبر مما ينبغي من فيزيمبرو، فقم بزيارة طبيب أو اذهب إلى المستشفى على الفور.

 

إذا نسيت تناول فيزيمبرو

إذا فاتتك إحدى الجرعات أو تقيأت، فتناول جرعتك التالية كما هو محدد. لا تتناول جرعة مضاعفة لتعويض القرص الذي نسيت تناوله.

 

إذا توقفت عن تناول فيزيمبرو

لا تتوقف عن تناول فيزيمبرو ما لم يخبرك طبيبك بذلك. إذا كانت لديك أي أسئلة أخرى حول استخدام هذا الدواء، فاسأل طبيبك أو الصيدلي أو الممرضة.

 

 

 

كما هو الحال بالنسبة لجميع الأدوية، يمكن أن يسبب هذا الدواء آثارًا جانبية، غير أنها لا تصيب الجميع.

 

تواصل مع طبيبك على الفور إذا لاحظت ظهور أي من الآثار الجانبية التالية - فقد تحتاج إلى علاج طبي عاجل:

·   التهاب الرئتين (شائع، قد يصيب ما يصل إلى شخص واحد من بين كل 10 أشخاص)

صعوبة في التنفس، ضيق التنفس، قد يصاحبهما سعال أو حمى. قد يعني هذا أنك مصاب بالتهاب في الرئتين يسمى المرض الرئوي الخلالي ويمكن أن يكون مميتًا.

·   الإسهال (شائع جدًا: قد يصيب أكثر من شخص واحد من بين كل 10 أشخاص)

قد يؤدي الإسهال إلى فقدان السوائل (شائع)، وانخفاض بوتاسيوم الدم (شائع جدًا)، وتدهور وظائف الكلى ويمكن أن يكون مميتًا. عند ظهور أولى علامات زيادة معدل تكرار حركة الأمعاء، تواصل مع طبيبك على الفور، واشرب كميات وفيرة من السوائل، وابدأ في استخدام علاج مضاد للإسهال في أقرب وقت ممكن. ينبغي أن يكون متاحًا لديك دواء مضاد للإسهال قبل أن تبدأ في تناول فيزيمبرو.

·   الطفح الجلدي (شائع جدًا)

من المهم علاج الطفح الجلدي في وقت مبكر. أخبر طبيبك إذا ظهر طفح جلدي. إذا لم يكن علاج الطفح الجلدي فعالًا أو إذا كان الطفح الجلدي يتفاقم (على سبيل المثال، أصبت بتقشر أو تشقق في الجلد)، ينبغي أن تخبر طبيبك على الفور، لأن طبيبك قد يقرر إيقاف علاجك بفيزيمبرو. قد يحدث الطفح الجلدي أو يتفاقم في المناطق المعرضة للشمس. يوصى بالوقاية من الشمس عن طريق ارتداء ملابس واقية واستخدام كريم واقٍ من الشمس.

 

أخبر طبيبك في أقرب وقت ممكن إذا لاحظت أيًا من الآثار الجانبية الأخرى التالية:

 

شائعة جدًا (قد تصيب أكثر من شخص واحد من بين كل 10 أشخاص):

·   التهاب الفم والشفتين

·   مشكلات الأظافر

·   جفاف الجلد

·   فقدان الشهية

·   جفاف العينين أو احمرارهما أو إصابتهما بالحكة

·   فقدان الوزن

·   تساقط الشعر

·   الحكة

·   نتائج غير طبيعية لفحوصات الدم الخاصة بإنزيمات الكبد

·   الغثيان أو القيء

·   احمرار أو ألم في راحتي اليدين أو باطن القدمين

·   التعب

·   الضعف

·   تشقق الجلد

 

شائعة (قد تصيب ما يصل إلى شخص واحد من بين كل 10 أشخاص):

·   تغير في حاسة التذوق

·   تقشر الجلد

·   التهاب العينين

·   زيادة نمو شعر الجسم بشكل غير طبيعي

 

الإبلاغ عن الآثار الجانبية

إذا أصبت بأي آثار جانبية، فتحدث إلى طبيبك أو الصيدلي أو الممرضة. يتضمن هذا أي آثار جانبية محتملة غير مدرجة في هذه النشرة. يمكنك أيضًا الإبلاغ عن الآثار الجانبية مباشرةً إلى المركز الوطني للتيقظ . بالإبلاغ عن الآثار الجانبية، يمكنك المساعدة في توفير المزيد من المعلومات حول سلامة هذا الدواء.

 

 

للإبلاغ عن الآثار الجانبية

 

·    المملكة العربية السعودية

 

المركز الوطني للتيقظ الدوائي (NPC)

·    مركز الاتصال الموحد: 19999

·    البريد الإلكتروني: npc.drug@sfda.gov.sa

·    الموقع الإلكتروني: https://ade.sfda.gov.sa/

 

 

·   دول الخليج الأخرى:

 

-        الرجاء الاتصال بالمؤسسات والهيئات الوطنية في كل دولة.

 

يحفظ في درجة حرارة أقل من ٣٠ درجة مئوية.

 

بعد فتح العبوة: يحفظ في درجة حرارة اقل من ٣٠ درجة مئوية ويستخدم خلال ١٠٠ يوم من تاريخ فتح العبوة .                       

 

احتفظ بهذا الدواء بعيدًا عن مرأى ومتناول الأطفال.

 

لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المُدون على العبوة الكرتونية وشريط البليستر بعد الرمز "EXP". يشير تاريخ انتهاء الصلاحية إلى آخر يوم في الشهر المذكور.

 

قد يشكّل هذا الدواء خطرًا على البيئة. لا تتخلص من أي أدوية عبر مياه الصرف أو مع المخلفات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد تستخدمها. ستساعد هذه التدابير على حماية البيئة.

 

-                 المادة الفعالة هي داكوميتينيب (في صورة داكوميتينيب أحادي الهيدرات). تأتي أقراص فيزيمبرو المغلفة بطبقة رقيقة بتركيزات مختلفة.

قرص فيزيمبرو ١٥ ملجم: يحتوي كل قرص مغلف بطبقة رقيقة على ١٥ ملجم من داكوميتينيب

قرص فيزيمبرو ٣٠ ملجم: يحتوي كل قرص مغلف بطبقة رقيقة على ٣٠ ملجم من داكوميتينيب

قرص فيزيمبرو ٤٥ ملجم: يحتوي كل قرص مغلف بطبقة رقيقة على ٤٥ ملجم من داكوميتينيب

-                 المكونات الأخرى هي:

أساس القرص: لاكتوز أحادي الهيدرات، سيليولوز بلوري مكروي، جليكولات نشا الصوديوم، ستيارات المغنيسيوم (انظر القسم ٢ "يحتوي فيزيمبرو على لاكتوز وصوديوم").

الطبقة المغلِفة الرقيقة: أوبادري II أزرق اللون 85F30716 يحتوي على كحول البولي فينيل - متحلل مائيًا بشكل جزئي (E1203)، تلك (E553b)، ثاني أكسيد التيتانيوم (E171)، ماكروجول (E1521)، ليك الألومنيوم القرمزي النيلي (E132).

 

-          تتوفر أقراص فيزيمبرو 15 ملجم المغلفة بطبقة رقيقة في صورة أقراص زرقاء مغلفة بطبقة رقيقة، دائرية الشكل محدبة الوجهين، ومحفور عليها "Pfizer" على أحد الجانبين و"DCB15" على الجانب الآخر.

 

-            تتوفر أقراص فيزيمبرو 30 ملجم المغلفة بطبقة رقيقة في صورة أقراص زرقاء مغلفة بطبقة رقيقة، دائرية الشكل محدبة الوجهين، ومحفور عليها "Pfizer" على أحد الجانبين و"DCB30" على الجانب الآخر.

 

-            تتوفر أقراص فيزيمبرو 45 ملجم المغلفة بطبقة رقيقة في صورة أقراص زرقاء مغلفة بطبقة رقيقة، دائرية الشكل محدبة الوجهين، ومحفور عليها "Pfizer" على أحد الجانبين و"DCB45" على الجانب الآخر.

 

يتاح فيزيمبرو في عبوات تحتوي على 30 قرصًا مغلفًا بطبقة رقيقة (أقراص).

 

مالك رخصة التسويق

Pfizer Inc

66 Hudson Boulevard East, NY 10001

New York, United Sates of America

 

الشركة الصانعة

Pfizer Manufacturing Deutschland GmbH

Betriebsstätte Freiburg

Mooswaldallee 1

79090 Freiburg

Germany، ألمانيا

 

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

Vizimpro 15 mg film-coated tablets Vizimpro 30 mg film-coated tablets Vizimpro 45 mg film-coated tablets

Vizimpro 15 mg film-coated tablets Each film-coated tablet contains dacomitinib monohydrate equivalent to 15 mg dacomitinib. Excipients with known effect Each film-coated tablet contains 40 mg of lactose monohydrate. Vizimpro 30 mg film-coated tablets Each film-coated tablet contains dacomitinib monohydrate equivalent to 30 mg dacomitinib. Excipients with known effect Each film-coated tablet contains 81 mg of lactose monohydrate. Vizimpro 45 mg film-coated tablets Each film-coated tablet contains dacomitinib monohydrate equivalent to 45 mg dacomitinib. Excipients with known effect Each film-coated tablet contains 121 mg of lactose monohydrate. For the full list of excipients, see section 6.1.

Film-coated tablet (tablet). Vizimpro 15 mg film-coated tablets Blue film-coated, 6.35 mm, round biconvex tablet, debossed with “Pfizer” on one side and “DCB15” on the other. Vizimpro 30 mg film-coated tablets Blue film-coated, 7.5 mm, round biconvex tablet, debossed with “Pfizer” on one side and “DCB30” on the other. Vizimpro 45 mg film-coated tablets Blue film-coated, 9.0 mm, round biconvex tablet, debossed with “Pfizer” on one side and “DCB45” on the other.

 

Vizimpro, as monotherapy, is indicated for the first-line treatment of adult patients with locally advanced or metastatic non‑small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)‑activating mutations.


Treatment with Vizimpro should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.

 

EGFR mutation status should be established prior to initiation of dacomitinib therapy (see section 4.4).

 

Posology

 

The recommended dose of Vizimpro is 45 mg taken orally once daily, until disease progression or unacceptable toxicity occurs.

 

Patients should be encouraged to take their dose at approximately the same time each day. If the patient vomits or misses a dose, an additional dose should not be taken and the next prescribed dose should be taken at the usual time the next day.

 

Dose modifications

Dose modifications may be required based on individual safety and tolerability. If dose reduction is necessary, then the dose of Vizimpro should be reduced as described in Table 1. Dose modification and management guidelines for specific adverse reactions are provided in Table 2 (see sections 4.4 and 4.8).

 

Table 1.     Recommended dose modifications for Vizimpro adverse reactions

 

Dose level

Dose (once daily)

Recommended starting dose

45 mg

First dose reduction

30 mg

Second dose reduction

15 mg

 

Table 2.     Dose modification and management for Vizimpro adverse reactions

 

Adverse reactions

Dose modification

Interstitial lung disease (ILD/Pneumonitis)

·       Withhold dacomitinib during ILD/Pneumonitis diagnostic evaluation.

·       Permanently discontinue dacomitinib if ILD/Pneumonitis is confirmed.

Diarrhoea

 

·       For Grade 1 diarrhoea, no dose modification is required. Initiate treatment with anti-diarrhoeal medicinal products (e.g., loperamide) at first onset of diarrhoea. Encourage adequate oral fluid intake during diarrhoea.

·       For Grade 2 diarrhoea, if not improved to Grade ≤ 1 within 24 hours while using anti-diarrhoeal medicinal products (e.g., loperamide) and adequate oral fluid intake, withhold dacomitinib. Upon recovery to Grade ≤ 1, resume dacomitinib at the same dose level or consider a reduction of 1 dose level.

·       For Grade ≥ 3 diarrhoea, withhold dacomitinib. Treat with anti‑diarrhoeal medicinal products (e.g., loperamide), and adequate oral fluid intake or intravenous fluids or electrolytes as appropriate. Upon recovery to Grade ≤ 1, resume dacomitinib with a reduction of 1 dose level.

Skin-related adverse reactions

·       For Grade 1 rash or erythematous skin conditions, no dose modification is required. Initiate treatment (e.g., antibiotics, topical steroids, and emollients).

·       For Grade 1 exfoliative skin conditions, no dose modification is required. Initiate treatment (e.g., oral antibiotics and topical steroids).

·       For Grade 2 rash, erythematous or exfoliative skin conditions, no dose modification is required. Initiate treatment or provide additional treatment (e.g., oral antibiotics and topical steroids).

·       If Grade 2 rash, erythematous or exfoliative skin conditions persist for 72 hours despite treatment, withhold dacomitinib. Upon recovery to Grade ≤ 1, resume dacomitinib at the same dose level or consider a reduction of 1 dose level.

·       For Grade ≥ 3 rash, erythematous or exfoliative skin conditions, withhold dacomitinib. Initiate or continue treatment and/or provide additional treatment (e.g., broad spectrum oral or intravenous antibiotics and topical steroids). Upon recovery to Grade ≤ 1, resume dacomitinib with a reduction of 1 dose level.

Other

·       For Grade 1 or 2 toxicity, no dose modification is required.

·       For Grade ≥ 3 toxicity, withhold dacomitinib until symptoms resolve to Grade ≤ 2. Upon recovery, resume dacomitinib with a reduction of 1 dose level.

 

Special populations

 

Hepatic impairment

No starting dose adjustments are required when administering Vizimpro to patients with mild (Child‑Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. The starting dose of Vizimpro should be adjusted to 30 mg once daily in patients with severe (Child-Pugh class C) hepatic impairment. The dose may be increased to 45 mg once daily based on individual safety and tolerability after at least 4 weeks of treatment (see section 5.2).

 

Renal impairment

No starting dose adjustments are required when administering Vizimpro to patients with mild or moderate renal impairment (creatinine clearance [CrCl] ≥ 30 mL/min). Limited data are available in patients with severe renal impairment (CrCl < 30 mL/min). No data are available in patients requiring haemodialysis. Thus no dosing recommendations can be made for either patient population (see section 5.2).

 

Elderly population

No starting dose adjustment of Vizimpro in elderly (≥ 65 years of age) patients is required (see section 5.2).

 

Paediatric population

The safety and efficacy of Vizimpro in the paediatric population (< 18 years of age) have not been established. No data are available.

 

Method of administration

 

Vizimpro is for oral use. The tablets should be swallowed with water and can be taken with or without meals.


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

Assessment of EGFR mutation status

 

When assessing the EGFR mutation status of a patient, it is important that a well-validated and robust methodology is chosen to avoid false negative or false positive determinations.

 

Interstitial lung disease (ILD)/Pneumonitis

 

ILD/pneumonitis, which could be fatal, has been reported in patients receiving Vizimpro (see section 4.8). Patients with a history of ILD have not been studied.

 

Careful assessment of all patients with an acute onset or unexplained worsening of pulmonary symptoms (e.g., dyspnoea, cough, fever) should be performed to exclude ILD/pneumonitis. Treatment with dacomitinib should be withheld pending investigation of these symptoms. If ILD/pneumonitis is confirmed, dacomitinib should be permanently discontinued and appropriate treatment instituted as necessary (see section 4.2).

 

Diarrhoea

 

Diarrhoea, including severe diarrhoea, has been very commonly reported during treatment with Vizimpro (see section 4.8). Diarrhoea may result in dehydration with or without renal impairment, which could be fatal if not adequately treated.

 

Proactive management of diarrhoea should start at the first sign of diarrhoea especially within the first 2 weeks of starting dacomitinib, including adequate hydration combined with anti-diarrhoeal medicinal products and continued until loose bowel movements cease for 12 hours. Anti-diarrhoeal medicinal products (e.g., loperamide) should be used and, if necessary, escalated to the highest recommended approved dose. Patients may require dosing interruption and/or dose reduction of therapy with dacomitinib. Patients should maintain adequate oral hydration and patients who become dehydrated may require administration of intravenous fluids and electrolytes (see section 4.2).

 

Skin-related adverse reactions

 

Rash, erythematous and exfoliative skin conditions have been reported in patients treated with Vizimpro (see section 4.8).

 

For prevention of dry skin, initiate treatment with moisturizers, and upon development of rash, initiate treatment with topical antibiotics, emollients, and topical steroids. Start oral antibiotics and topical steroids in patients who develop exfoliative skin conditions. Consider adding broad spectrum oral or intravenous antibiotics if any of these conditions worsen to greater than or equal to Grade 2 severity. Rash, erythematous and exfoliative skin conditions may occur or worsen in areas exposed to the sun. Advise patients to use protective clothing and sunscreen before exposure to the sun. Patients may require dosing interruption and/or dose reduction of therapy with dacomitinib (see section 4.2).

 

Hepatotoxicity and transaminases increased

 

Transaminases increased (alanine aminotransferase increased, aspartate aminotransferase increased, transaminases increased) have been reported during treatment with Vizimpro (see section 4.8). Among NSCLC patients treated with dacomitinib 45 mg daily, there have been isolated reports of hepatotoxicity in 4 (1.6%) patients. Across the dacomitinib program, hepatic failure led to a fatal outcome in 1 patient. Therefore, periodic liver function testing is recommended. In patients who develop severe elevations in transaminases while taking dacomitinib, treatment should be interrupted (see section 4.2).

 

Medicinal products metabolised by cytochrome P450 (CYP)2D6

 

Vizimpro may increase exposure (or decrease exposure of active metabolites) of other medicinal products metabolised by CYP2D6. Concomitant use of medicinal products predominantly metabolised by CYP2D6 should be avoided unless such products are considered necessary (see section 4.5).

 

Other forms of interactions

 

Concomitant use of proton pump inhibitors (PPIs) with dacomitinib should be avoided (see section 4.5).

 

Lactose

 

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

 

Sodium

 

This medicinal product contains < 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium-free”.


Co-administration of dacomitinib with agents that increase gastric pH

 

The aqueous solubility of dacomitinib is pH dependent, with low (acidic) pH resulting in higher solubility. Data from a study in 24 healthy subjects indicated that co-administration of a single 45 mg dacomitinib dose with the PPI rabeprazole 40 mg once daily for 7 days decreased dacomitinib Cmax, AUC0-96h (area under the concentration-time curve from time 0 to 96 hours), and AUCinf (AUC from time 0 to infinity) (n=14) by approximately 51%, 39%, and 29%, respectively, when compared to a single 45 mg dose of dacomitinib administered alone. PPIs should be avoided while receiving treatment with dacomitinib (see section 4.4).

 

Based on data from observations in 8 patients from Study A7471001, there was no apparent effect of local antacid administration on Cmax and AUCinf of dacomitinib. Based on pooled data in patients, there was no apparent effect of histamine-2 (H2) receptor antagonists on steady-state trough concentration of dacomitinib (geometric mean ratio of 86% (90% CI: 73; 101). Local antacids and H2 receptor antagonists may be used if needed. Dacomitinib should be administered 2 hours before or at least 10 hours after taking H2 receptor antagonists.

 

Co-administration of dacomitinib and CYP2D6 substrates

 

Co-administration of single 45 mg oral dose of dacomitinib increased the mean exposure (AUClast and Cmax) of dextromethorphan, a probe CYP2D6 substrate, 855% and 874%, respectively, compared with administration of dextromethorphan alone. These results suggest that dacomitinib may increase exposure of other medicinal products (or decrease exposure to active metabolites) primarily metabolised by CYP2D6. Concomitant use of medicinal products predominantly metabolised by CYP2D6 should be avoided (see section 4.4). If concomitant use of such medicinal products is considered necessary, they should follow their respective labels for dose recommendation regarding co-administration with strong CYP2D6 inhibitors.

 

Effect of dacomitinib on drug transporters

 

Based on in vitro data, dacomitinib may have the potential to inhibit the activity of P‑glycoprotein (P‑gp) (in the gastrointestinal [GI] tract), Breast Cancer Resistance Protein (BCRP) (systemically and GI tract), and organic cation transporter (OCT)1 at clinically relevant concentrations (see section 5.2).

 

Effect of Strong CYP2D6 Inhibitors on Dacomitinib

Coadministration of a single 45 mg dose of VIZIMPRO with multiple doses of paroxetine (a strong CYP2D6 inhibitor) in healthy subjects increased the total AUClast of dacomitinib plus its active metabolite (O-desmethyl dacomitinib) in plasma by approximately 6%, which is not considered clinically relevant.


Woman of childbearing potential/Contraception

 

Women of childbearing potential should be advised to avoid becoming pregnant while receiving Vizimpro. Women of childbearing potential who are receiving this medicinal product should use adequate contraceptive methods during therapy and for at least 17 days (5 half-lives) after completing therapy.

 

Pregnancy

 

There are no data on the use of dacomitinib in pregnant women. Studies in animals have shown limited effects on reproductive toxicity (lower maternal body weight gain and food consumption in rats and rabbits, and lower foetal body weight and higher incidence of unossified metatarsals in rats only) (see section 5.3). Based on its mechanism of action, dacomitinib may cause foetal harm when administered to a pregnant woman. Dacomitinib should not be used during pregnancy. Female patients taking dacomitinib during pregnancy or who become pregnant while taking dacomitinib should be apprised of the potential hazard to the foetus.

 

Breast-feeding

 

It is not known whether dacomitinib and its metabolites are excreted in human milk. Because many medicinal products are excreted in human milk, and because of the potential for serious adverse reactions in breast‑fed infants from exposure to dacomitinib, mothers should be advised against breast‑feeding while receiving this medicinal product.

 

Fertility

 

Fertility studies have not been performed with dacomitinib. Non-clinical safety studies showed reversible epithelial atrophy in the cervix and vagina of rats (see section 5.3).


Vizimpro has minor influence on the ability to drive and use machines. Patients experiencing fatigue or ocular adverse reactions while taking dacomitinib should exercise caution when driving or operating machinery.

 


Summary of safety profile

 

The median duration of treatment with Vizimpro across the pooled data set was 66.7 weeks.

 

The most common (> 20%) adverse reactions in patients receiving dacomitinib were diarrhoea (88.6%), rash (79.2%), stomatitis (71.8%), nail disorder (65.5%), dry skin (33.3%), decreased appetite (31.8%), conjunctivitis (24.7%), weight decreased (24.3%), alopecia (23.1%), pruritus (22.4%), transaminases increased (22.0%), and nausea (20.4%).

 

Serious adverse reactions were reported in 6.7% of patients treated with dacomitinib. The most frequently (≥ 1%) reported serious adverse reactions in patients receiving dacomitinib were diarrhoea (2.0%), interstitial lung disease (1.2%), rash (1.2%), and decreased appetite (1.2%).

 

Adverse reactions leading to dose reductions were reported in 52.2% of patients treated with dacomitinib. The most frequently reported (> 5%) reasons for dose reductions due to any adverse reactions in patients receiving dacomitinib were rash (32.2%), nail disorder (16.5%), and diarrhoea (7.5%).

 

Adverse reactions leading to permanent discontinuation were reported in 6.7% of patients treated with dacomitinib. The most common (> 0.5%) reasons for permanent discontinuations associated with adverse reactions in patients receiving dacomitinib were: rash (2.4%), interstitial lung disease (2.0%), and diarrhoea (0.8%).

 

Tabulated list of adverse reactions

 

Table 3 presents adverse reactions for Vizimpro. Adverse reactions are listed according to system organ class (SOC). Within each SOC, the adverse reactions are ranked by frequency, with the most frequent reactions first, using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

 

 

Table 3.       Adverse reactions reported in dacomitinib clinical studies (N=255)

 

System organ class

Very common

Common

Metabolism and nutrition disorders

Decreased appetite

Hypokalaemiaa

Dehydration

Nervous system disorders

 

Dysgeusia

Eye disorders

Conjunctivitisb

Keratitis

Respiratory, thoracic and mediastinal disorders

 

Interstitial lung disease*c

Gastrointestinal disorders

Diarrhoea*

Stomatitisd

Vomiting

Nausea

 

Skin and subcutaneous tissue disorders

Rashe

Palmar-plantar erythrodysaesthesia syndrome

Skin fissures

Dry skinf

Pruritusg

Nail disorderh

Alopecia

Skin exfoliationi

Hypertrichosis

 

General disorders and administration site conditions

Fatigue

Asthenia

 

Investigations

Transaminases increasedj

Weight decreased

 

Data based on pool of 255 patients who received Vizimpro 45 mg once daily as starting dose for first-line treatment of NSCLC with EGFR-activating mutations across clinical studies.

 

*  Fatal events were reported.

a    Hypokalaemia includes the following preferred terms (PTs): Blood potassium decreased, Hypokalaemia.

b    Conjunctivitis includes the following PTs: Blepharitis, Conjunctivitis, Dry eye, Noninfective     conjunctivitis.

c    Interstitial lung disease includes the following PTs: Interstitial lung disease, Pneumonitis.

d    Stomatitis includes the following PTs: Aphthous ulcer, Cheilitis, Dry mouth, Mucosal inflammation,     Mouth ulceration, Oral pain, Oropharyngeal pain, Stomatitis.

e    Rash (also referred to as Rash and erythematous skin conditions) includes the following PTs: Acne,     Dermatitis acneiform, Erythema, Erythema multiforme, Rash, Rash erythematous, Rash generalised, Rash     macular, Rash maculo-papular, Rash papular.

f     Dry skin includes the following PTs: Dry skin, Xerosis.

g    Pruritus includes the following PTs: Pruritus, Rash pruritic.

h    Nail disorder includes the following PTs: Ingrowing nail, Nail bed bleeding, Nail bed inflammation, Nail     discolouration, Nail disorder, Nail infection, Nail toxicity, Onychoclasis, Onycholysis, Onychomadesis,     Paronychia.

i     Skin exfoliation (also referred to as Exfoliative skin conditions) includes the following PTs: Exfoliative     rash, Skin exfoliation.

j     Transaminases increased includes the following PTs: Alanine aminotransferase increased, Aspartate aminotransferase increased, Transaminases increased.

 

Description of selected adverse reactions

 

Very common adverse reactions in patients occurring in at least 10% of patients in Study ARCHER 1050 are summarised by National Cancer Institute-Common Toxicity Criteria (NCI‑CTC) Grade in Table 4.

 

Table 4.        Very common adverse reactions in Phase 3 Study ARCHER 1050 (N=451)

 

 

Dacomitinib

(N=227)

Gefitinib

(N=224)

Adverse Reactionsa

All Grades

%

Grade 3

%

Grade 4

%

All Grades

%

Grade 3

%

Grade 4

%

Metabolism and nutrition disorders

Decreased appetite

30.8

3.1

0.0

25.0

0.4

0.0

Hypokalaemiab

10.1

4.0

0.9

5.8

1.8

0.0

Eye disorders

Conjunctivitisc

23.3

0.0

0.0

8.9

0.0

0.0

Gastrointestinal disorders

Diarrhoead

87.2

8.4

0.0

55.8

0.9

0.0

Stomatitise

69.6

4.4

0.4

33.5

0.4

0.0

Nausea

18.9

1.3

0.0

21.9

0.4

0.0

Skin and subcutaneous tissue disorders

Rashf

77.1

24.2

0.0

57.6

0.9

0.0

Palmar-plantar erythrodysaesthesia syndrome

14.5

0.9

0.0

3.1

0.0

0.0

Dry sking

29.5

1.8

0.0

18.8

0.4

0.0

Pruritush

20.3

0.9

0.0

14.3

1.3

0.0

Nail disorderi

65.6

7.9

0.0

21.4

1.3

0.0

Alopecia

23.3

0.4

0.0

12.5

0.0

0.0

General disorders and administration site conditions

Asthenia

12.8

2.2

0.0

12.5

1.3

0.0

Investigations

Transaminases increasedj

23.8

0.9

0.0

40.2

9.8

0.0

Weight decreased

25.6

2.2

0.0

16.5

0.4

0.0

a Only adverse reactions with ≥ 10% incidence in the dacomitinib arm are included.

Hypokalaemia includes the following preferred terms (PTs): Blood potassium decreased, Hypokalaemia.

c   Conjunctivitis includes the following PTs: Blepharitis, Conjunctivitis, Dry eye, Noninfective conjunctivitis.

1 fatal event was reported in the dacomitinib arm.

e   Stomatitis includes the following PTs: Aphthous ulcer, Cheilitis, Dry mouth, Mucosal inflammation, Mouth ulceration, Oral pain, Oropharyngeal pain, Stomatitis.

f   Rash includes the following PTs: Acne, Dermatitis acneiform, Erythema, Rash, Rash erythematous, Rash generalised, Rash macular, Rash maculo-papular, Rash papular.

g   Dry skin includes the following PTs: Dry skin, Xerosis.

Pruritus includes the following PTs: Pruritus, Rash pruritic.

i   Nail disorder includes the following PTs: Ingrowing nail, Nail discolouration, Nail disorder, Nail infection, Nail toxicity, Onychoclasis, Onycholysis, Onychomadesis, Paronychia.

j   Transaminases increased includes the following PTs: Alanine aminotransferase increased, Aspartate aminotransferase increased, Transaminases increased.

 

Interstitial lung disease (ILD)/Pneumonitis

ILD/pneumonitis adverse reactions were reported in 2.7% of patients receiving Vizimpro, and Grade ≥ 3 ILD/pneumonitis adverse reactions were reported in 0.8%, including a fatal event (0.4%) (see section 4.4).

 

The median time to the first episode of any grade ILD/pneumonitis was 16 weeks and the median time to the worst episode of ILD/pneumonitis was 16 weeks in patients receiving dacomitinib. The median duration of any grade and Grade ≥ 3 ILD/pneumonitis was 13 weeks and 1.5 weeks, respectively (see section 4.4).

 

Diarrhoea

Diarrhoea was the most frequently reported adverse reaction in patients receiving Vizimpro (88.6%) and Grade ≥ 3 diarrhoea adverse reactions were reported in 9.4% of patients. In a clinical study, one patient (0.4%) had a fatal outcome (see section 4.4).

 

The median time to the first episode of any grade diarrhoea was 1 week and the median time to the worst episode of diarrhoea was 2 weeks in patients receiving dacomitinib. The median duration of any grade and Grade ≥ 3 diarrhoea was 20 weeks and 1 week, respectively (see section 4.4).

 

Skin-related adverse reactions

Rash, erythematous and exfoliative skin condition adverse reactions were reported in 79.2% and 5.5%, respectively, of patients receiving Vizimpro. Skin-related adverse reactions were Grades 1 to 3. Grade 3 rash and erythematous skin condition adverse reactions were the most frequently reported Grade 3 adverse reactions (25.5%). Grade 3 exfoliative skin conditions were reported in 0.8% of patients (see section 4.4).

 

The median time to the first episode of any grade rash and erythematous skin conditions was approximately 2 weeks and the median time to the worst episode of rash and erythematous skin conditions was 7 weeks in patients receiving dacomitinib. The median duration of any grade and Grade ≥ 3 rash and erythematous skin conditions was 53 weeks and 2 weeks, respectively. The median time to the first episode of any grade exfoliative skin conditions was 6 weeks and the median time to the worst episode of exfoliative skin conditions was 6 weeks. The median duration of any grade and Grade ≥ 3 exfoliative skin conditions was 10 weeks and approximately 2 weeks, respectively.

 

Transaminases increased

Transaminases increased (alanine aminotransferase increased, aspartate aminotransferase increased, transaminases increased) were reported in 22.0% of patients receiving Vizimpro and were Grades 1 to 3, with the majority Grade 1 (18.4%) (see section 4.4).

 

The median time to the first episode of any grade of transaminases increased was approximately 12 weeks and the median time to the worst episode of transaminases increased was 12 weeks in patients receiving dacomitinib. The median duration of any grade and Grade ≥ 3 transaminases increased was 11 weeks and 1 week, respectively.

 

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 to National Pharmacovigilance Centre (NPC).

 

To report any side effects:

 

·     Saudi Arabia

 

National Pharmacovigilance Centre (NPC)

·         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.


The adverse reactions observed at doses greater than 45 mg once daily were primarily gastrointestinal, dermatological, and constitutional (e.g., fatigue, malaise, and weight loss).

 

There is no known antidote for dacomitinib. The treatment of dacomitinib overdose should consist of symptomatic treatment and general supportive measures.

 


Pharmacotherapeutic group: Anti-neoplastic agents, protein kinase inhibitors, ATC code: L01EB07

 

Mechanism of action

 

Dacomitinib is a pan-human epidermal growth factor receptor (HER) (EGFR/HER1, HER2, and HER4) inhibitor, with activity against mutated EGFR with deletions in exon 19 or the L858R substitution in exon 21. Dacomitinib binds selectively and irreversibly to its HER family targets thereby providing prolonged inhibition.

 

Clinical efficacy

 

Vizimpro in first‑line treatment of NSCLC patients with EGFR-activating mutations (ARCHER 1050)

The efficacy and safety of Vizimpro was studied in a Phase 3 study (ARCHER 1050) conducted in patients with locally advanced, not amenable to curative surgery or radiotherapy, or metastatic NSCLC harbouring activating mutations of EGFR, to demonstrate the superiority of dacomitinib versus gefitinib. A total of 452 patients were randomised 1:1 to dacomitinib or gefitinib in a multicentre, multinational, randomised, open‑label Phase 3 study.

 

Treatment was administered orally on a continuous daily basis until disease progression, institution of new anticancer therapy, intolerable toxicity, withdrawal of consent, death, or investigator decision dictated by protocol compliance, whichever occurred first. Stratification factors at randomisation were race (Japanese versus mainland Chinese versus other East Asian versus non-East Asian, as stated by the patient), and EGFR mutation status (exon 19 deletion versus the L858R mutation in exon 21). EGFR mutation status was determined by a standardised and commercially available test kit.

 

The primary endpoint of the study was progression-free survival (PFS) as determined by blinded Independent Radiology Central (IRC) review. Key secondary endpoints included objective response rate (ORR), duration of response (DoR), and overall survival (OS).

 

The demographic characteristics of the overall study population were 60% female; median age at enrolment was 62 years with 10.8% being ≥ 75 years old. Thirty percent had baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 and 70% had ECOG PS 1; 59% had an exon 19 deletion, and 41% had a L858R mutation in exon 21. Race was 23% White, 77% Asian, and < 1% Black. Patients with brain metastases or leptomeningeal disease or ECOG PS ≥ 2 were excluded from the study.

 

A statistically significant improvement in PFS as determined by the IRC was demonstrated for patients randomised to dacomitinib compared with those randomised to gefitinib, see Table 5 and Figure 1. Subgroup analyses of PFS per IRC review based on baseline characteristics were consistent with those from the primary analysis of PFS. In particular, the hazard ratios (HRs) for PFS per IRC review in Asian and non-Asian patients were 0.509 (95% CI: 0.391, 0. 662) and 0.889 (95% CI: 0.568, 1.391), respectively. In Asian patients, median PFS was 16.5 months for dacomitinib arm and 9.3 months for gefitinib arm. In non-Asian patients, median PFS was 9.3 months for dacomitinib arm and 9.2 months for gefitinib arm.

 

OS results from the final analysis (data cut-off date of 17-Feb-2017) when 48.7% of events had occurred showed a HR of 0.760 (95% CI: 0.582, 0.993) and a gain of 7.3 months in median OS (median OS: 34.1 months [95% CI: 29.5, 37.7] and 26.8 months [95% CI: 23.7, 32.1] in the dacomitinib and gefitinib arm, respectively). However, according to the hierarchical testing approach, the analysis was stopped with the testing of ORR as the statistical significance was not reached. Therefore, the statistical significance of OS improvement could not be formally assessed.

 

Table 5.       Efficacy results from ARCHER 1050 in patients with previously untreated NSCLC with EGFR-activating mutations – ITT population

 

Dacomitinib

N=227

Gefitinib

N=225

Progression-Free Survival (per IRC)

 

Number of patients with event, n (%)

136 (59.9%)

179 (79.6%)

Median PFS in months (95% CI)

14.7 (11.1, 16.6)

9.2 (9.1, 11.0)

HR (95% CI)a

0.589 (0.469, 0.739)

2-sided p-valueb

< 0.0001

Objective Response Rate (per IRC)

 

Objective Response Rate % (95% CI)

74.9% (68.7, 80.4)

71.6% (65.2, 77.4)

2-sided p-valuec

0.3883

Duration of Response in Responders (per IRC)

 

Number of responders per IRC review, n (%)

170 (74.9)

161 (71.6)

Median DoR in months (95% CI)

14.8 (12.0, 17.4)

8.3 (7.4, 9.2)

HR (95% CI)a

0.403 (0.307, 0.529)

2-sided p-valueb

< 0.0001

⃰ Data based on data cut-off date of 29 July 2016.

Abbreviations: CI=confidence interval; EGFR=epidermal growth factor receptor; HR=hazard ratio; IRC=independent radiologic central; ITT=Intent-to-treat; IWRS=interactive web response system; N/n=total number; NSCLC=non-small cell lung cancer; PFS=progression-free survival; DoR=Duration of Response.

a. From stratified Cox Regression. The stratification factors were Race (Japanese vs mainland Chinese and other East Asian vs non-East Asian) and EGFR mutation status (exon 19 deletion vs the L858R mutation in exon 21) at randomisation per IWRS.

b. Based on the stratified log-rank test. The stratification factors were Race (Japanese vs mainland Chinese and other East Asian vs non-East Asian) and EGFR mutation status (exon 19 deletion vs the L858R mutation in exon 21) at randomisation per IWRS.

c. Based on the stratified Cochran-Mantel-Haenszel test. The stratification factors were Race (Japanese vs mainland Chinese and other East Asian vs non-East Asian) and EGFR mutation status (exon 19 deletion vs the L858R mutation in exon 21) at randomisation per IWRS.

 

Figure 1.     ARCHER 1050 - Kaplan-Meier curve for PFS per IRC review – ITT population

 

Abbreviations: CI=confidence interval; HR=hazard ratio; IRC=independent radiologic central; ITT=Intent‑To‑Treat; N=total number; PFS=progression-free survival.

 

Paediatric population

 

The European Medicines Agency has waived the obligation to submit the results of studies with dacomitinib in all subsets of the paediatric population in NSCLC indication (see section 4.2 for information on paediatric use).

 


Absorption

 

Following the administration of a single 45 mg dose of dacomitinib tablets, the mean oral bioavailability of dacomitinib is 80% (range: 65% to 100%) compared to intravenous administration, with Cmax occurring 5 to 6 hours after oral dosing. Following dacomitinib 45 mg daily dosing, steady‑state was reached within 14 days. Food does not alter bioavailability to a clinically meaningful extent. Dacomitinib is a substrate for the membrane transport proteins P-gp and BCRP. However, based on the oral bioavailability of 80%, these membrane transport proteins are unlikely to have any impact on dacomitinib absorption.

 

Distribution

 

Dacomitinib is extensively distributed throughout the body with a mean steady‑state volume of distribution of 27 L/kg (patient of 70 kg) [coefficient of variation (CV%): 18%] following intravenous administration. In plasma, dacomitinib binds to albumin and a1-acid glycoprotein and the fraction unbound is approximately 2% in vitro and ex vivo in healthy volunteers.

 

Biotransformation

 

In humans, dacomitinib undergoes oxidation and glutathione conjugation as the major metabolic pathways. Following oral administration of a single 45‑mg dose of [14C] dacomitinib, the most abundant circulating metabolite was O-desmethyl dacomitinib. This metabolite exhibited in vitro pharmacologic activity that was similar to that of dacomitinib in the in vitro biochemical assays. In faeces, dacomitinib, O-desmethyl dacomitinib, a cysteine conjugate of dacomitinib, and a mono‑oxygenated metabolite of dacomitinib were the major drug-related components. In vitro studies indicated that CYP2D6 was the major CYP isozyme involved in the formation of O-desmethyl dacomitinib, while CYP3A4 contributed to the formation of other minor oxidative metabolites. O‑desmethyl dacomitinib accounted for 16% of human plasma radioactivity and is formed mainly by CYP2D6 and to a lesser extent CYP2C9. The inhibition of CYP2D6 translated into approximately a 90% reduction in metabolite exposure and an approximate 37% increase in dacomitinib exposure.

 

Other information on drug-drug interactions

 

Effect of dacomitinib and O-desmethyl dacomitinib on CYP enzymes

In vitro, dacomitinib and its metabolite O-desmethyl dacomitinib have a low potential to inhibit the activities of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A4/5 at clinically relevant concentrations. In vitro, dacomitinib has a low potential to induce CYP1A2, CYP2B6, or CYP3A4 at clinically relevant concentrations.

 

Effect of dacomitinib on drug transporters

In vitro, dacomitinib has a low potential to inhibit the activities of drug transporters P-gp (systemically), organic anion transporters (OAT)1 and OAT3, OCT2, organic anion transporting polypeptide (OATP)1B1, and OATP1B3, but may inhibit the activity of P‑gp (in the GI tract), BCRP (systemically and GI tract), and OCT1 at clinically relevant concentrations.

 

Effect of dacomitinib on UGT Enzymes

In vitro, dacomitinib has a low potential to inhibit uridine‑diphosphate glucuronosyltransferase (UGT)1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15.

 

Elimination

 

The plasma half-life of dacomitinib ranges from 54 to 80 hours. Dacomitinib showed a clearance of 20.0 L/hr with an inter-individual variability of 32% (CV%). In 6 healthy male subjects given a single‑oral dose of [14C] radiolabeled dacomitinib, a median of 82% of the total administered radioactivity was recovered in 552 hours; faeces (79% of dose) was the major route of excretion, with 3% of the dose recovered in urine, of which < 1% of the administered dose was unchanged dacomitinib.

 

Special populations

 

Age, race, gender, body weight

Based on population pharmacokinetic analyses, patient age, race (Asian and non-Asian), gender, and body weight do not have a clinically relevant effect on predicted steady-state exposure of dacomitinib. Approximately 90% of patients included in this analysis were Asian or White.

 

Hepatic impairment

In a dedicated hepatic impairment study, following a single‑oral dose of 30 mg Vizimpro, dacomitinib exposure (AUCinf and Cmax) was unchanged in mild hepatic impairment (Child‑Pugh class A; N=8) and decreased by 15% and 20%, respectively in moderate hepatic impairment (Child‑Pugh class B; N=9) when compared to subjects with normal hepatic function (N=8). In a second dedicated hepatic impairment study, following a single‑oral dose of 30 mg Vizimpro, dacomitinib exposure was unchanged for AUCinf and increased by 31% for Cmax in subjects with severe hepatic impairment (Child-Pugh class C; N=8), when compared to subjects with normal hepatic function (N=8). In addition, based on a population pharmacokinetic analysis using data from 1381 patients, that included 158 patients with mild hepatic impairment defined by National Cancer Institute (NCI) criteria [total bilirubin ≤ Upper Limit of Normal (ULN) and Aspartate Aminotransferase (AST) > ULN, or total bilirubin > 1.0 to 1.5 × ULN and any AST; N=158], mild hepatic impairment had no effect on the pharmacokinetics of dacomitinib. From the small number of patients in the moderate group [total bilirubin > 1.5 to 3 × ULN and any AST; N=5], there is no evidence for a change in dacomitinib pharmacokinetics.

 

Renal impairment

No clinical studies have been conducted in patients with impaired renal function. Based on population pharmacokinetic analyses, mild (60 mL/min ≤ CrCl < 90 mL/min; N=590) and moderate (30 mL/min ≤ CrCl < 60 mL/min; N=218) renal impairment, did not alter dacomitinib pharmacokinetics, relative to subjects with normal (CrCl ≥ 90 mL/min; N=567) renal function. Limited pharmacokinetic data are available in patients with severe renal impairment (CrCl < 30 mL/min) (N=4). The pharmacokinetics in patients requiring haemodialysis have not been studied.

 

Exposure response relationships

No clear relationship between dacomitinib exposure and efficacy could be characterised over the exposure range studied. Significant exposure-safety relationship was defined for Grade ≥ 3 rash/dermatitis acneiform, other skin toxicities, diarrhoea and Grade ≥ 1 stomatitis.


Repeated-dose toxicity

 

In oral repeated-dose toxicity studies for up to 6 months in rats and 9 months in dogs, the primary toxicities were identified in the skin/hair (dermal changes in rats and dogs, atrophy/dysplasia of hair follicles in rats), kidney (papillary necrosis often accompanied by tubular degeneration, regeneration, dilatation and/or atrophy and changes in urinary markers indicative of renal injury in rats, erosion or ulceration of the pelvic epithelium with associated inflammation without changes indicative of renal dysfunction in dogs), eye (cornea epithelial atrophy in rats and dogs, corneal ulcers/erosions with red/swollen conjunctiva(e), conjunctivitis, elevated third eyelid, increased squinting, partially closed eyes, lacrimation, and/or ocular discharge in dogs), and digestive system (enteropathy in rats and dogs, erosions/ulcers of the mouth with reddened mucous membranes in dogs), and atrophy of epithelial cells of other organs in rats. In addition, hepatocellular necrosis with transaminase increases and hepatocellular vacuolation were observed in rats only. These effects were reversible with the exception of hair follicles and kidney changes. All effects occurred at systemic exposure below that in humans at the recommended dose of 45 mg once daily.

 

Genotoxicity

 

Dacomitinib was tested using a series of genetic toxicology assays. Dacomitinib was not mutagenic in a bacterial reverse mutation (Ames) assay, and not clastogenic or aneugenic in the in vivo bone marrow micronucleus assay in male and female rats. Dacomitinib was clastogenic in the in vitro human lymphocyte chromosome aberration assay at cytotoxic concentrations. Dacomitinib is not directly reactive toward DNA as evidenced by the negative response in the bacterial reverse mutation assay and did not induce chromosome damage in a bone marrow micronucleus assay at concentrations up to approximately 60-70 times the unbound AUC or Cmax at the recommended human dose. Thus, dacomitinib is not expected to be genotoxic at clinically relevant exposure concentrations.

 

Carcinogenicity

 

Carcinogenicity studies have not been performed with dacomitinib.

 

Impairment of fertility

 

Fertility studies have not been performed with dacomitinib. In repeat-dose toxicity studies with dacomitinib, effects on reproductive organs were observed in female rats given approximately 0.3 times the unbound AUC at the recommended human dose (for 6 months) and were limited to reversible epithelial atrophy in the cervix and vagina. There was no effect on reproductive organs in male rats given ≤ 2 mg/kg/day for 6 months (approximately 1.1 times the unbound AUC at the recommended human dose), or in dogs given ≤ 1 mg/kg/day for 9 months (approximately 0.3 times the unbound AUC at the recommended human dose).

 

Developmental toxicity

 

In embryo-foetal development studies in rats and rabbits, pregnant animals received oral doses up to approximately 2.4 times and 0.3 times, respectively, the unbound AUC at the recommended human dose during the period of organogenesis. Maternal body weight gain and food intake were lower in pregnant rats and rabbits. The maternally toxic dose was foetotoxic in rats, resulting in reduced foetal body weights and higher incidence of unossified metatarsals. 

 

Phototoxicity

 

A phototoxicity study with dacomitinib in pigmented rats showed no phototoxicity potential.

 

Environmental risk assessment

 

Environmental risk assessment studies have shown that dacomitinib has the potential to be very persistent, bioaccumulative and toxic to the environment (see section 6.6).

 


Tablet core

 

Lactose monohydrate

Microcrystalline cellulose

Sodium starch glycolate

Magnesium stearate

 

Film coating

 

Opadry II Blue 85F30716 containing:

Polyvinyl alcohol – partially hydrolysed (E1203)

Talc (E553b)

Titanium dioxide (E171)

Macrogol (E1521)

Indigo carmine aluminium lake (E132)


Not applicable.


Do not use VIZIMPRO after the expiry date which is stated on the carton / Blister / Bottle / Vial label after EXP:. The expiry date refers to the last day of that month. Shelf life : 5 years.

Store below 30°C.

 

After opening store below 30°C and use it within 100 days

 


HDPE bottle with dessicant contains 30 tablets.

 


Dacomitinib has the potential to be a very persistent, bioaccumulative and toxic substance (see section 5.3). Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

 


Pfizer Inc. 66 Hudson Boulevard East, NY 10001, New York, United Sates of America Manufactured by Pfizer Manufacturing Deutschland GmbH Betriebsstatte, Freiburg, Germany

December 2023
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