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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)

Balversa is a prescription medicine belongs to a group of medicines called Kinase Inhibitors. Different kinase enzymes exist in human cells and they help control important functions, such as cell signaling, metabolism, division, and survival. Certain kinases are more active in some types of cancer cells and blocking them may help keep the cancer cells from growing.

 

Balversa is indicated to treat bladder cancer (urothelial cancer) that has spread or cannot be removed by surgery in adult patients:

 

□  whose cancer has a certain type of abnormal “FGFR” gene. and

□  who have tried at least one other chemotherapy medicine that contains platinum, and it did not work or is no longer working.

 

Your doctor will test your cancer for certain types of abnormal FGFR genes and make sure that Balversa is right for you.

Balversa is for use in adults only.


1.  Do not take Balversa and tell your doctor if:

 

·      You are allergic to Erdafitinib or to any of the inactive ingredients mentioned in section 6.

 

 

Warnings and precautions

 

·      Eye problems. Eye problems are common with Balversa but can also be serious. Eye problems include dry or inflamed eyes, inflamed cornea (front part of the eye) and disorders of the retina, an internal part of the eye. Tell your doctor right away if you develop blurred vision, loss of vision or other visual changes. You should use artificial tear substitutes, hydrating or lubricating eye gels or ointments at least every 2 hours during waking hours to help prevent dry eyes. During treatment with Balversa, your doctor will send you to see an eye specialist.

 

·         High phosphate levels in the blood (hyperphosphatemia). Hyperphosphatemia is common with Balversa but can also be serious. High levels of phosphate in your blood may lead to build-up of minerals such as calcium in different tissues in your body. Your doctor will check your blood phosphate level between 14 and 21 days after starting treatment with Balversa, and then monthly. 

Your doctor may prescribe changes in your diet or phosphate lowering therapy, or change or stop treatment with Balversa if needed.

Tell your doctor right away if you develop painful skin lesions, any muscle cramps, or numbness or tingling around your mouth.

 

Talk to your doctor before taking Balversa if you:

 

·         Have vision or eye problems.

·         Have or have had a renal disorder.

·         Have or have had a hepatic disorder.

·         Are pregnant or plan to become pregnant. Balversa can harm your unborn baby. You should not become pregnant during treatment with Balversa.

·         Are a male with a female partner who can become pregnant (see under section 2 “pregnancy & breastfeeding and fertility”)

·         Breastfeeding or planning to breast feed.

·         You are taking any medicine that contains phosphate such as some medicines used for heartburn (antacids containing phosphates), vitamin D and phosphate supplements.

 

Tell your doctor immediately if during treatment you suffer from:

 

-           Problems with your vision such as blurred vision, loss of vision or other visual changes.

-           If you develop any nail or mucous or skin problems including nails separating from the nail bed, nail pain, nail bleeding, breaking of the nails, color or texture changes in your nails, infected skin around the nail, an itchy skin rash, dry skin, or cracks in the skin

 

Your doctor may need to adjust your dose of Balversa or will decide to stop treatment.

 

You should keep in regular contact with your doctor. From time to time, your doctor may need to do blood, urine, eye tests, to set the right dose of Balversa for you.

 

Other medicines and Balversa

 

Please tell your doctor if you are taking, have recently taken other medicines even those obtained without a prescription and herbal preparations. This is because other drugs can affect the way Balversa works and the way it is removed from the body and Balversa can affect the way other drugs work as well.

 

In particular, you should tell your doctor if you are taking or have recently taken medicines like:

 

·    antifungals (e.g. ketoconazole, fluconazole, itraconazole, voriconazole)

·    antibiotics used to treat infections (e.g. clarithromycin)

·    some drugs used to treat tuberculosis (e.g. Rifampicin)

·    HIV protease inhibitors (e.g. ritonavir, nelfinavir, indinavir)

·    nilotinib and imatinib (used to treat certain cancers)

·    phosphate-containing antacid, used to treat heartburn

·    Antiepileptic medicines (e.g. phenytoin or carbamazepine).

·    herbal preparations containing St. John’s Wort (Hypericum perforatum)

·    Phosphate supplements.

 

Taking Balversa with food and drink

 

Not relevant

 

Children and adolescents

 

The use of Balversa is not recommended in children and adolescents.

 

Use in pregnancy and lactation and fertility

 

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

Your doctor may do a pregnancy test before you start treatment with Balversa.

·         You should use effective birth control during treatment and for 1 month after the last dose of BALVERSA.

·         Talk to your doctor about birth control methods that may be right for you.

·         Tell your doctor right away if you become pregnant or think you may be pregnant.

 

Breastfeeding

 

Do not breastfeed during treatment and for 1 month after the last dose of Balversa.

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

 

Male with female partner who can become pregnant

 

You should use effective birth control when sexually active during treatment with Balversa and for 1 month after the last dose.

 

Fertility

 

This drug can affect fertility in females. If this is a concern for you, discuss with your doctor.

 

Driving and using machines

 

Do not drive or use any tools or machines if you feel dizzy or sleepy, or have problems seeing clearly after taking Balversa.

·      You are allergic to Erdafitinib or to any of the inactive ingredients mentioned in section 6.

 


Always take Balversa as your doctor told you exactly. You should check with your doctor or pharmacist if you are not sure.

This medicine should only be prescribed for you by a doctor with experience in the treatment of cancer.

 

How much Balversa do I have to take

The recommended starting dose of Balversa is 8 mg (two 4 mg tablets) orally once daily, with a dose increase to 9 mg (three 3 mg tablets) once daily based on serum phosphate (PO4) levels and your tolerance measured at 14 to 21 days.

 

Following the initiation of your treatment with this medicine, frequent blood tests will be taken by your doctor to define the correct dose. Afterwards regular blood tests by your doctor will be required to adjust the dose from time to time.

 

How should I take the Balversa tablets

 

•       Take Balversa once daily on the same time of the day, preferably in the morning to ensure consistent and maximal drug absorption.

•       Swallow Balversa whole with fluid (preferably water); do not chew, divide, or crush the tablets.

 

How long should I take Balversa

 

You will need to take Balversa every day as long as your doctor told you. You should keep in regular contact with your doctor.

 

If you take more Balversa than you should

 

If you have accidentally taken too much Balversa contact your doctor or go to the nearest hospital emergency department immediately and take this package insert with you.

 

If you forget to take Balversa

 

·   If you miss a dose of Balversa, take the missed dose as soon as possible on the same day. Take your regular dose of Balversa the next day. Do not take more Balversa than prescribed to make up for the missed dose.

·   If you vomit after taking Balversa, do not take another Balversa tablet. Take your regular dose of Balversa the next day.

 

If you stop taking Balversa

 

Do not stop your treatment unless your doctor tells you to do so.

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


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

 

Contact your doctor immediately, should you experience severe allergic reaction (rare side effect) with symptoms like rash, itching, swelling of the face or tongue or throat, severe dizziness and trouble breathing.

 

The following side effects has been reported with Balversa:

 

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

 

•          High  level of phosphate in the blood

•          decreased appetite

•          low level of sodium in the blood

•          sores in the mouth

•          diarrhea

•          dry mouth

•          dry skin

•          hair loss

•          redness, swelling, peeling or tenderness, mainly on the hands or feet (‘hand-foot syndrome’)

•          nails separating from the bed

•          infected skin around the nail

•          poor nail formation

•          discolored nails

•          dry eyes

•          inflamed eyes

•          change in sense of taste with food tasting metallic, sour, or bitter.

•          weight loss

•          increased level of ‘creatinine’ in the blood

 

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

 

•          nail problems

•          base of the nails separate from the nail bed

•          nail pain

•          itching

•          crack in the skin

•          ridging of nails

•          breaking of the nails

•          itchy skin rash (eczema)

•          thickened skin

•          flaky skin

•          abnormal growth or appearance on the skin

•          fluid build-up under the retina, which can lead to blurred vision

•          retina separates from the layers of cells within, which can lead to blurred vision

•          inflamed cornea (front part of the eye)

•          retina separates from the back of the eye, which may lead to vision loss (detached retina)

•          swelling of the retina

•          disease of the retina

•          ulcers on the cornea (front part of the eye)

•          a gel-like substance separates from the retina

•          nasal dryness

•          membrane dryness (including nose, mouth, eyes, vagina)

•          very dry skin

•          bleeding under the nail

•          itchy skin rash with round spots (eczema nummular)

•          the ‘macula’ (center of the retina) separates from the layers of cells within, which can lead to blurred vision

•          thinning of the skin

•          skin reaction

•          nail discomfort.

•          nose bleeds

•          sudden decrease in kidney function

 

The side effects listed below have also been reported with the use of Balversa:

•          deposits of calcium in the blood vessels, which can lead to blood clots, skin ulcers and serious infections

•          deposits of calcium in the skin

 

 

Reporting of side effects

 

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your healthcare professional or pharmacist.

 


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 label after ‘EXP’. The expiry date refers to the last day of that month.

Do not store above 30°C

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.


Active ingredient:

 

The active ingredient is Erdafitinib which is supplied as 3 mg, 4 mg or 5 mg film-coated tablets for oral administration.

 

Inactive ingredients:

Tablet Core: Croscarmellose sodium, Magnesium stearate (from vegetable source), Mannitol, Meglumine, and Microcrystalline Cellulose.

 

Film Coating: (Opadry amb II): Glycerol monocaprylocaprate Type I, Polyvinyl alcoholpartially hydrolyzed, Sodium lauryl sulfate, Talc, Titanium dioxide, Iron oxide yellow, Iron oxide red (for the orange and brown tablets only), Ferrosoferric oxide/iron oxide black (for the brown tablets only).

 


3 mg: Yellow, round biconvex, film-coated, debossed with “3” on one side; and “EF” on the other side. Bottle of 56-tablets with child resistant closure. Bottle of 84-tablets with child resistant closure. 4 mg: Orange, round biconvex, film-coated, debossed with “4” on one side; and “EF” on the other side. Bottle of 28-tablets with child resistant closure. Bottle of 56-tablets with child resistant closure. 5 mg: Brown, round biconvex, film-coated, debossed with “5” on one side; and “EF” on the other side. Bottle of 28-tablets with child resistant closure.

Marketing authorization holder

Janssen Biotech inc

800 850 Ridgeview Drive

Horsham United States

Manufacturer:

Janssen-Cilag SpA, Latina, Italy


To contact us, please visit our website www.janssen.com/contact-us This leaflet was last revised on 05 July 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)

بالفيرسا هو دواء يُصرف بوصفة طبية ينتمي إلى مجموعة من الأدوية تُسمّى مُثبّطات الكيناز. توجد إنزيمات الكيناز المختلفة في الخلايا الإنسان وتساعد في التحكم بالوظائف المهمة ، مثل إشارة الخلية ، والتمثيل الغذائي، والانقسام، والبقاء على قيد الحياة. يكثر نشاط بعض أنواع إنزيمات الكيناز في بعض أنواع الخلايا السرطانية وقد يساعد تثبيطها في منع نمو خلايا السرطان

بالفيرسا مُعد للاستخدام في علاج سرطان المثانة (سرطان الظهارة البولية) المنتشر أو الذي لا يمكن إزالته عن طريق الجراحة للمرضى البالغين :

• الذين لديهم سرطان  يحتوي على نوع معين من الجين "FGFR" غير الطبيعي ، و

• الذين جربوا دواءً واحدًا على الأقل من العلاج الكيميائي الذي يحتوي على البلاتين، ولم ينجح أو لم يعد  فعالاً.

سيقوم طبيبك بإجراء فحص للسرطان لديك للبحث عن نوع معين من الجين "FGFR" غير الطبيعي وليتأكد من أنّ دواء بالفيرسا مناسب لك.

يستخدم بالفيرسا للبالغين فقط.

لا تتناول بالفيرسا وأخبر طبيبك إذا:

• كان لديك حساسية من إردافِتنيب أو من أيّ من المكونات غير الفعالة  المذكورة في القسم 6.

التحذيرات والإحتياطات

مشاكل العين. مشاكل العين شائعة مع بالفيرسا ولكنها يمكن أن تكون خطيرة أيضًا. تشمل مشاكل العين جفاف أو التهاب العيون، والتهاب القرنية (الجزء الأمامي من العين) واضطرابات الشبكية، وهي جزء داخلي من العين. أخبر طبيبك فورًا إذا أُصبت بعدم وضوح الرؤية، أو فقدان الرؤية أو تغيّرات بصرية أخرى. يجب عليك استخدام بدائل الدموع الاصطناعية أو جِل مُرطب أو مُزلِق للعين أو مرهم كل ساعتين على الأقل خلال ساعات الاستيقاظ  للمساعدة في منع حدوث جفاف العيون. أثناء العلاج ببالفيرسا، سوف يقوم طبيبك بإحالتك إلى أخصائي العيون.

•  مستويات عالية من الفوسفات في الدم (فرط فوسفات الدم) فرط فوسفات الدم هو أمر شائع حدوثه مع بالفيرسا  ولكن يمكن أن يكون خطيرًا. يمكن أن تؤدي المستويات المرتفعة من الفوسفات في الدم إلى تراكم المعادن مثل الكالسيوم في الأنسجة المختلفة في جسمك. سيقوم طبيبك بفحص مستوى الفوسفات في دمك  بين 14 و21 يومًا بعد بدء العلاج ببالفيرسا ومن ثم شهريًا.

 قد يصف طبيبك تغييرات في نظامك الغذائي أو علاج خافض للفوسفات، أو تغير أو وقف العلاج ببالفيرسا إذا لزم الأمر.

أخبر طبيبك على الفور إذا أصبت بآفات جلدية مؤلمة أو أي تشنج في العضلات أو تنميل أو وخز حول فمك.


تحدث إلى طبيبك قبل تناول بالفيرسا إذا:

• كان لديك مشاكل في الرؤية أو في العين.

• كنت تعاني أو عانيت في السابق من اضطراب في الكلى.

• كنت تعاني أو عانيت في السابق من اضطراب في الكبد.

• كنتِ حاملاً أو تخططين للحمل. يمكن أن يضر بالفيرسا  طفلك الذي لم يولد بعد .  لا يجب أن تحملي أثناء علاجك ببالفيرسا.

• رجلاً ولديك شريكة أنثى قادرة على الحمل (انظر القسم 2 أدناه "الحمل والرضاعة الطبيعية والخصوبة")

• كنتِ ترضعين رضاعة طبيعية أو تخططين للرضاعة الطبيعية

• كنت تتناول أي دواء يحتوي على الفوسفات مثل بعض الأدوية المستخدمة لحموضة المعدة (مضادات الحموضة التي تحتوي على الفوسفات) وفيتامين د ومكملات الفوسفات.

أخبر طبيبك على الفور إذا كنت تعاني أثناء العلاج أيًّا مما يلي:

-  مشاكل في الرؤية مثل عدم وضوح الرؤية، وفقدان الرؤية أو اضطرابات بصرية أخرى.

- إذا ظهرت لديك أي مشاكل في الأظافر أو في الأغشية المخاطية أو الجلد بما في ذلك انفصال الأظافر عن فراش الظفر، ألم الأظافر ، نزيف الأظافر ، تكسرالأظافر، تغيرات في  لون أو ملمس أظافرك، جلد مصاب حول الظفر، طفح جلدي مع حكة، جفاف الجلد، أو تشققات في الجلد.
 

قد يحتاج طبيبك إلى تعديل جرعة بالفيرسا أو إيقاف العلاج.

يجب أن تبقى على اتصال دائم مع طبيبك. قد يحتاج طبيبك من وقت لآخر القيام بفحوصات للدم والبول وفحص العيون لتحديد الجرعة المناسبة لك من بالفيرسا.
 

 

أدوية أخرى و بالفيرسا

يرجى إخبار طبيبك إذا كنت تتناول، أو تناولت أدوية أخرى مؤخرًا بما فيها تلك التي يتم الحصول عليها بدون وصفة طبية والمستحضرات العشبية. وذلك لأن الأدوية الأخرى يمكن أن تؤثر على طريقة عمل بالفيرسا وعلى طريقة إزالته من الجسم كما يمكن أن يؤثر بالفيرسا على طريقة عمل الأدوية الأخرى.

على الأخص؛ يجب أن تخبر طبيبك إذا كنت تتناول أو إذا تناولت مؤخراً أدوية مثل:

• مضادات الفطريات (مثل الكيتوكونازول ، الفلوكونازول ، الإيتراكونازول ، الفوريكونازول)

• المضادات الحيوية المستخدمة لعلاج العدوى (مثل كلاريثروميسين)

• بعض الأدوية المستخدمة لعلاج السل (مثل ريفامبيسين)

• مثبطات البروتيز العكسي لفيروس  نقص المناعة البشرية (مثل ريتونافير، نلفينافير، إندينافير)

• نيلوتينيب وإماتينيب (يستخدمان لعلاج بعض أنواع السرطان)

• مضادات الحموضة المحتوية على الفوسفات، والتي تستخدم لعلاج حموضة المعدة

• الأدوية المضادة للصرع (مثل الفينيتوين أو كاربامازيبين).

• مستحضرات عشبية تحتوي على نبتة سانت جون (هايبريكام بيرفوراتام)

• مكملات الفوسفات.


تناول بالفيرسا مع الطعام والشراب

غير ذات صلة
 

الأطفال والمراهقين

لا ينصح باستخدام بالفيرسا لدى الأطفال والمراهقين.

 

الاستخدام اثناء الحمل والرضاعة والخصوبة

إذا كنتِ حاملاً أو مرضعة، أو تعتقدين أنك قد تكونين حاملاً أو تخططين لإنجاب طفل، استشيري طبيبك أو الصيدلي قبل تناول هذا الدواء.

الحمل

قد يقوم طبيبك بإجراء اختبار للحمل قبل أن تبدأي العلاج ببالفيرسا.

•          يجب عليك استخدام وسيلة فعّالة لمنع الحمل أثناء العلاج ولمدة شهر واحد بعد الجرعة الأخيرة من بالفيرسا.

•          تحدثي إلى طبيبك حول طرق منع الحمل التي قد تكون مناسبة لك.

•          أخبري طبيبك على الفور إذا أصبحتِ حاملا أو تعتقدين أنك حامل.

الرضاعة الطبيعية

لا ترضعي طفلك رضاعة طبيعية أثناء علاجك ببالفيرسا ولمدة شهر واحد بعد آخر جرعة منه.

استشيري طبيبك أو الصيدلي قبل تناول أي دواء.

رجل مع شريكة أنثى التي يمكن أن تصبح حاملا

يجب عليك استخدام وسائل منع الحمل الفعالة عند ممارسة النشاط الجنسي خلال فترة العلاج ببالفيرسا  ولمدة شهر واحد بعد آخر جرعة.

الخصوبة

هذا الدواء يمكن أن يؤثر على الخصوبة عند الإناث. إذا كان هذا يُقلقكِ، فاستشيري طبيبك.
 

القيادة واستخدام الآلات

لا تقود السيارة أو تستخدم أي أدوات أو آلات إذا شعرت بالدوار أو النعاس، أو تعاني من  مشاكل في الرؤية الواضحة  بعد تناول بالفيرسا.

https://localhost:44358/Dashboard

تناول بالفيرسا دائمًا كما شرح لك طبيبك بالضبط . يجب عليك استشارة طبيبك أو الصيدلي إذا كنت غير متأكداً.

يجب أن يوصف لك هذا الدواء فقط من قبل طبيب لديه خبرة في علاج السرطان.

كم هي جرعة بالفيرسا التي يجب أن أتناولها

جرعة البدء الموصى بها من بالفيرسا هي 8 مجم (قرصان 4 مجم) عن طريق الفم مرة واحدة يوميًا، مع زيادة الجرعة إلى 9 مجم (ثلاثة أقراص 3 مجم) مرة واحدة يوميًا بناءً على مستويات الفوسفات (PO4)  لديك في الدم  وعلى قياس مدى تحملك للدواء من 14 إلى 21 يوماً من بدء العلاج.

بعد بدء علاجك بهذا الدواء، سيقوم طبيبك بإجراء فحوصات دم متكررة لتحديد الجرعة الصحيحة. بعد ذلك، سيطلب منك طبيبك  إجراء فحوصات دم منتظمة لتعديل الجرعة من وقت لآخر.

 

كيف أتناول أقراص بالفيرسا

• تناول بالفيرسا مرة واحدة يوميًا في نفس الوقت من اليوم، ويفضل أن يكون ذلك في الصباح لضمان امتصاص الدواء بشكل ثابت ولأقصى حد.

• ابتلع أقراص بالفيرسا بالكامل مع شراب (يفضل ماء)؛ لا تمضغ أو تقسم أو تسحق الأقراص.

كم من الوقت يجب أن أتناول ببالفيرسا

ستحتاج إلى تناول بالفيرسا كل يوم طالما أخبرك طبيبك بذلك. يجب أن تبقى على اتصال منتظم مع طبيبك.

إذا تناولت بالفيرسا أكثر مما يجب

إذا تناولت بالفيرسا أكثر مما يجب عن طريق الخطأ، فاتصل بطبيبك أو اذهب إلى أقرب قسم طوارئ في المستشفى على الفور واحضر نشرة معلومات الدواء هذه معك.

إذا نسيت أن تتناول بالفيرسا

• إذا فاتتك جرعة من بالفيرسا، فتناول الجرعة الفائتة في أقرب وقت ممكن في نفس اليوم. تناول جرعتك  المعتادة من بالفيرسا في اليوم التالي. لا تتناول جرعة إضافية من بالفيرسا لتعويض الجرعة الفائتة.

• إذا تقيأت بعد تناول بالفيرسا، فلا تتناول قرص آخر منه. تناول جرعتك  المعتادة من بالفيرسا في اليوم التالي.


إذا توقفت عن تناول بالفيرسا

لا تتوقف عن علاجك إلا إذا أخبرك طبيبك بذلك.

إذا كان لديك أي أسئلة أخرى حول استخدام هذا الدواء، فاسأل طبيبك أو الصيدلي.

كما هو الحال مع سائر الأدوية، يمكن أن يسبب إردافِتنيب أعراضًا جانبية على الرغم من أنها لا تحدث لدى الجميع.

راجع طبيبك على الفور، إذا تعرّضت للحساسية الشديدة (عرَض جانبي نادر) مع أعراض مثل الطفح الجلدي والحكة وتورم في الوجه أو اللسان أو الحلق، والدوخة الشديدة وصعوبة في التنفس.


تم الإبلاغ عن الأعراض الجانبية التالية أثناء العلاج ببالفيرسا:

أعراض جانبية شائعة جدًا (قد تؤثر على أكثر من شخص من كل 10 أشخاص):

•          زيادة مستوى الفوسفات في الدم

•          قلة الشهية

•          انخفاض مستوى الصوديوم في الدم

•          تقرحات الفم

•          إسهال

•          جفاف الفم

•          جفاف الجلد

•          تساقط شعر

•          احمرار أو تورم أو تقشير أو  تحسس ، خاصة على اليدين أو القدمين ("متلازمة اليد والقدم")

•          انفصال الأظافر عن فراشها

•          التهاب الجلد حول الظفر

•          ضعف تشكيل الظفر

•          تغيّر في لون الأظافر

•          جفاف العيون

•          التهاب العيون

•          تغير في حاسة التذوق حيث يكون طعم  الطعام معدني أو حامض أو مر

•          فقدان الوزن

•          ارتفاع مستوى ‘الكرياتينين’ في الدم


أعراض جانبية شائعة (قد تؤثر على ما يصل إلى 1 من كل 10 أشخاص):

•          مشاكل في الأظافر

•          انفصال قاعدة الأظافر من فراش الظفر

•          ألم في الظفر

•          حكّة

•          تشقّق الجلد

•          تخطيط الأظافر

•          تكسّر الأظافر

•          طفح جلدي مصحوب بحكّة (إكزيما)

•          زيادة في سماكة الجلد

•          تقشّر الجلد

•          نمو أو مظهر غير طبيعي على الجلد

•          تراكم السوائل تحت الشبكية مما قد يؤدي إلى عدم وضوح الرؤية

•          انفصال الشبكية عن طبقات الخلايا داخلها مما قد يؤدي إلى عدم وضوح الرؤية

•          التهاب القرنية (الجزء الأمامي من العين)

•          انفصال الشبكية عن الجزء الخلفي من العين، مما قد يؤدي إلى فقدان البصر (فصل الشبكية)

•          تورم الشبكية

•          مرض شبكية العين

•          تقرحات على  القرنية (الجزء الأمامي من العين)

•          انفصال المادة التي تشبه الهلام عن الشبكية

•          جفاف الأنف

•          جفاف الأغشية (بما في ذلك الأنف والفم والعينين والمهبل)

•          جلد جاف جدًا

•          نزيف تحت الظفر

•          طفح جلدي يسبب حكة مع بقع مستديرة (أكزيما قطرية).

•          انفصال "البُقعة" (مركز الشبكية) عن طبقات الخلايا داخلها، مما قد يؤدي إلى عدم وضوح الرؤية

•          ترقق الجلد

•          تفاعلات جلدية

•          الشعور بعدم الراحة في الأظافر

•          نزيف الأنف

•          انخفاض مفاجئ في وظيفة الكلى

 

تم الإبلاغ عن الأعراض الجانبية المذكورة أدناه مع استخدام بالفيرسا:

•          ترسب الكالسيوم في الأوعية الدموية، والتي يمكن أن تؤدي إلى تجلط الدم وتقرحات الجلد وعدوى خطيرة

•          ترسب الكالسيوم في الجلد

 

الإبلاغ عن الأعراض الجانبية

إن كان لديك أعراض جانبية أو لاحظت أعراض جانبية غير مذكورة في هذه النشرة، فضلًا ابلغ اخصائي الرعاية الصحية أو الصيدلي.

يُحفظ هذا الدواء بعيدا عن مرأى ومتناول الأطفال.

لا تستخدم هذا الدواء بعد تاريخ انتهاء الصلاحية المذكور على العلبة والملصق بعد كلمة "EXP". يشير تاريخ انتهاء الصلاحية إلى اليوم الأخير من ذلك الشهر.

احفظه في درجة حرارة لا تزيد عن 30 درجة مئوية.

لا تتخلص من أي أدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية التي لم تعد تستخدمها. هذه التدابير سوف تساعد في حماية البيئة.
 

 

العنصر الفعال:

العنصر الفعال هو إردافِتنيب على شكل أقراص مُغلّفة بغشاء رقيق يحتوي كل منها على 3 مجم أو 4 مجم أو 5 مجم للتناول عن طريق الفم.

مكونات غير فعالة:

لب القرص: كروس كارميلوز الصوديوم، ستيرات المغنيسيوم (من مصدر نباتي)، مانيتول، ميغلومين، سليولوز ميكروكريستالين.

طبقة الغشاء الرقيق: (أوبادري أمب II): النوع الأول من جليسيرول مونوكابريلوكابرات، كحول البولي فينيل - المتحلل جزئياً، لوريل سلفات الصوديوم، التالك ، ثاني أكسيد التيتانيوم، أكسيد الحديد الأصفر، أكسيد الحديد الأحمر (للأقراص البرتقالية والبنيّة فقط)، أكسيد الحديدوز الحديدي /أكسيد الحديد الأسود (للأقراص البنية فقط).

الشكل الصيدلاني لبالفيرسا ووصفه وحجم عبوته

العبوة  أقراص 3 مجم: أقراص صفراء، مُحدّبة الوجهين، مستديرة، مُغلّفة بغشاء رقيق نُقش على أحد جانبيها الرقم  "3"؛ و الحروف "EF" على الجانب الآخر.

الأقراص مُعبأة في قارورة تحتوي على 56 حبة مع غطاء مقاوم لعبث الأطفال.

الأقراص مُعبأة في قارورة تحتوي على 84 حبة مع غطاء مقاوم لعبث الأطفال.

 

أقراص 4 مجم: أقراص برتقالية، مُحدّبة الوجهين، مستديرة، مُغلّفة بغشاء رقيق نُقش على أحد جانبيها الرقم  "4"؛ و الحروف "EF" على الجانب الآخر.

الأقراص مُعبأة في قارورة تحتوي على 28 حبة مع غطاء مقاوم لعبث الأطفال.

الأقراص مُعبأة في قارورة تحتوي على 56 حبة مع غطاء مقاوم لعبث الأطفال.

 

أقراص 5 مجم: أقراص بُنّية اللون، مُحدّبة الوجهين، مستديرة، مُغلّفة بغشاء رقيق نُقش على أحد جانبيها الرقم  "5"؛ و الحروف "EF" على الجانب الآخر.

الأقراص مُعبأة في قارورة تحتوي على 28 حبة مع غطاء مقاوم لعبث الأطفال.

قد لا تسوّق جميع أحجام العبوات.

حامل رخصة التسويق

جانسن بايوتيك انك 800 850 ريدجيفيو هورشام، الولايات المتحدة الأمريكية

المُصنّع

جانسن – سيلاج إس.بي.إيه، لاتينا، إيطاليا

للاتصال بنا من خلال: www.janssen.com/contact-us تمت آخر مراجعة لهذه النشرة بتاريخ 5 يوليو 2023.
 Read this leaflet carefully before you start using this product as it contains important information for you

Balversa 3mg tablets. Balversa 4mg tablets. Balversa 5mg tablets

Erdafitinib 3mg tablets. Erdafitinib 4mg tablets. Erdafitinib 5mg tablets. Excipient(s) with known effects None For the full list of excipients, see section 6.1. Excipient(s) with known effects None For the full list of excipients, see section 6.1.

3 mg tablets: Yellow, round biconvex, film-coated, debossed with “3” on one side and “EF” on the other side. Available in Bottle of 56-tablets and 84-tablets with child resistant closure. 4 mg tablets: Orange, round biconvex, film-coated, debossed with “4” on one side and “EF” on the other side. Available in Bottle of 28 and 56 tablets with child resistant closure. 5 mg tablets: Brown, round biconvex, film-coated, debossed with “5” on one side and “EF” on the other side. Available in Bottle of 28-tablets with child resistant closure.

Balversa is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC), that has:

·      susceptible FGFR3 or FGFR2 genetic alterations, and

·      progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Balversa is for adult use only.


The recommended starting dose of Balversa is 8 mg (two 4 mg tablets) orally once daily, with a dose increase to 9 mg (three 3 mg tablets) once daily based on serum phosphate (PO4) levels and tolerability at 14 to 21 days.

 

Method of administration

 

Before taking BALVERSA, patients must have confirmation of certain FGFR gene alterations as confirmed by a validated test.

 

Swallow tablets whole with or without food. If vomiting occurs any time after taking Balversa, the next dose should be taken the next day. Treatment should continue until disease progression or unacceptable toxicity occurs.

 

Missed dose

 

If a dose of Balversa is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for Balversa the next day. Extra tablets should not be taken to make up for the missed dose.

 

Dose Increase based on Serum Phosphate Levels

 

Assess serum phosphate levels 14 to 21 days after initiating treatment. Increase the dose of BALVERSA to 9 mg once daily if serum phosphate level is < 5.5 mg/dL and there are no ocular disorders or Grade 2 or greater adverse reactions. Monitor phosphate levels monthly for hyperphosphatemia.

 

The recommended dose modifications for adverse reactions are listed in the table below:

 

Dose

1st dose reduction

2nd dose reduction

3rd dose reduction

4th dose reduction

5th dose reduction

9 mg →

(Three 3mg tabs)

8 mg

(two 4 mg tablets)

6 mg

(two 3 mg tablets)

5 mg

(one 5 mg tablet)

4 mg

(one 4 mg tablet)

stop

 

 

 

 

 

 

8 mg

(two 4 mg tablets)

6 mg

(two 3 mg tablets)

5 mg

(one 5 mg tablet)

4 mg

(one 4 mg tablet)

stop

 

 

 

The following table summarizes recommendations for dose interruption, reduction, or discontinuation of Balversa in the management of specific adverse reactions.

 

Adverse Reaction

BALVERSA Dose Modification

Hyperphosphatemia

In all patients, restrict phosphate intake to 600-800 mg daily. If serum phosphate is above 7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate level returns to < 5.5 mg/dL.

5.6-6.9 mg/dL (1.8-2.3

mmol/L)

Continue Balversa at current dose.

7.0-9.0 mg/dL (2.3-2.9

mmol/L)

Withhold Balversa with weekly reassessments until level returns to

< 5.5 mg/dL (or baseline). Then restart Balversa at the same dose

level. A dose reduction may be implemented for hyperphosphatemia lasting > 1 week.

> 9.0 mg/dL (> 2.9 mmol/L)

Withhold Balversa with weekly reassessments until level returns to

< 5.5 mg/dL (or baseline). Then may restart Balversa at 1 dose level lower.

> 10.0 mg/dL (> 3.2 mmol/L) or significant alteration in baseline renal function or

Grade 3 hypercalcemia

Withhold Balversa with weekly reassessments until level returns to

< 5.5 mg/dL (or baseline). Then may restart Balversa at 2 dose levels lower.

Central Serous Retinopathy/Retinal Pigment Epithelial Detachment (CSR/RPED)

Grade 1: Asymptomatic; clinical or diagnostic observations only

Withhold until resolution. If resolves within 4 weeks, resume at the next lower dose level. Then, if no recurrence for a month, consider reescalation.

If stable for 2 consecutive eye exams but not resolved, resume at the next lower dose level.

Grade 2: Visual acuity 20/40 or

better or ≤ 3 lines of decreased vision from baseline

Withhold until resolution. If resolves within 4 weeks, may resume at the next lower dose level.

Grade 3: Visual acuity worse than 20/40 or > 3 lines of

decreased vision from baseline

Withhold until resolution. If resolves within 4 weeks, may resume two dose levels lower. If recurs, consider permanent

discontinuation.

Grade 4: Visual acuity 20/200 or

worse in affected eye

Permanently discontinue.

Other Adverse Reactions a

Grade 3

Withhold BALVERSA until resolves to Grade 1 or baseline, then

may resume dose level lower.

Grade 4

Permanently discontinue.

 

a           Dose adjustment graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEv4.03).


Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1

Ocular Disorders

 

Balversa can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) resulting in visual field defect.

 

CSR/RPED was reported in 25% of patients treated with Balversa, with a median time to first onset of 50 days. Grade 3 CSR/RPED, involving central field of vision, was reported in 3% of patients. CSR/RPED resolved in 13% of patients and was ongoing in 13% of patients at the study cutoff. CSR/RPED led to dose interruptions and reductions in 9% and 14% of patients, respectively and 3% of patients discontinued Balversa.

 

Dry eye symptoms occurred in 28% of patients during treatment with Balversa and were Grade 3 in 6% of patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed.

 

Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms.

 

Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography.

 

Withhold Balversa when CSR occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 in severity. For ocular adverse reactions, follow the dose modification guidelines [see Posology and method of administration (4.2)].

 

Hyperphosphatemia and Soft Tissue Mineralization

 

Balversa can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non- uremic calciphylaxis and vascular calcification. Increases in phosphate levels are a pharmacodynamic effect of Balversa [see Pharmacodynamics (5.1)].

Hyperphosphatemia was reported as adverse reaction in 76% of patients treated with Balversa. The median onset time for any grade event of hyperphosphatemia was 20 days (range: 8 –116) after initiating Balversa. Thirty-two percent of patients received phosphate binders during treatment with Balversa.

 

Cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification have been observed in 0.3% of patients treated with Balversa.

 

Monitor for hyperphosphatemia throughout treatment. In all patients, restrict phosphate intake to 600- 800 mg daily. If serum phosphate is above 7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate level returns to <5.5 mg/dL. Withhold, dose reduce, or permanently discontinue Balversa based on duration and severity of hyperphosphatemia [see Posology and method of administration (4.2)]

 

Embryo-Fetal Toxicity

 

Based on the mechanism of action and findings in animal reproduction studies, BALVERSA can cause fetal harm when administered to a pregnant woman. In an embryo-fetal toxicity study, oral administration of erdafitinib to pregnant rats during the period of organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum human recommended dose based on area under the curve (AUC). Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA and for one month after the last dose [see mechanism of action (5.1) and fertility, pregnancy and lactation (4.6)]


Drug Interaction Studies

 

Clinical Studies and Model-Based Approaches

 

Moderate CYP2C9 Inhibitors:

 

Erdafitinib mean ratios (90% CI) for Cmax and AUCinf were 121% (99.9, 147) and 148% (120, 182), respectively, when co-administered with fluconazole, a moderate CYP2C9 and CYP3A4 inhibitor, relative to erdafitinib alone.

 

Strong CYP3A4 Inhibitors:

 

Erdafitinib mean ratios (90% CI) for Cmax and AUCinf were 105% (86.7, 127) and 134% (109, 164), respectively, when co-administered with itraconazole (a strong CYP3A4 inhibitor and P-gp inhibitor) relative to Erdafitinib alone.

 

Strong CYP3A4/2C9 Inducers:

 

Simulations suggested that rifampicin (a strong CYP3A4/2C9 inducer) may significantly decrease Erdafitinib Cmax and AUC.

 

In vitro Studies:

 

CYP Substrates:

 

Erdafitinib is a time dependent inhibitor and inducer of CYP3A4. The effect of erdafitinib on a sensitive CYP3A4 substrate is unknown. Erdafitinib is not an inhibitor of other major CYP isozymes at clinically relevant concentrations.

 

Transporters:

 

Erdafitinib is a substrate and inhibitor of P-gp. P-gp inhibitors are not expected to affect erdafitinib exposure to a clinically relevant extent. Erdafitinib is an inhibitor of OCT2.

 

Erdafitinib does not inhibit BCRP, OATP1B, OATP1B3, OAT1, OAT3, OCT1, MATE-1, or MATE-2K at clinically relevant concentrations.

 

Acid-Lowering Agents:

 

Erdafitinib has adequate solubility across the pH range of 1 to 7.4. Acid-lowering agents (e.g., antacids, H2-antagonists, proton pump inhibitors) are not expected to affect the bioavailability of erdafitinib.

 

Interactions can be summarized as follows: Effect of other drugs on Balversa

 

 

Moderate CYP2C9 or strong CYP3A4 Inhibitors

Clinical Impact

·    Co-administration of Balversa with moderate CYP2C9

or strong CYP3A4 inhibitors increased Erdafitinib plasma concentrations.

·    Increased Erdafitinib plasma concentrations may lead to increased drug- related toxicity [see Warnings and Precautions (4.4)].

Clinical management

·  Consider alternative therapies that are not strong inhibitors of moderate CYP2C9 or strong CYP3A4 inhibitors during treatment with Balversa.

·    If co-administration of a moderate CYP2C9 or strong CYP3A4 inhibitors is unavoidable, monitor closely for adverse reactions and consider dose modifications accordingly [see posology and method of administration (4.2)]. If the strong inhibitor is discontinued, Balversa dose may be

increased in the absence of drug-related toxicity.

Strong CYP2C9 or CYP3A4 Inducers

Clinical Impact

·     Co-administration of Balversa with strong inducers of CYP2C9 or CYP3A4 may decrease Erdafitinib plasma concentrations significantly.

·     Decreased Erdafitinib plasma concentrations may lead to decreased activity.

Clinical management

·   Avoid co-administration of strong inducers of CYP2C9 or CYP3A4 with Balversa

Moderate CYP2C9 or CYP3A4 Inducers

Clinical Impact

·   Co-administration of Balversa with moderate inducers of CYP2C9 or CYP3A4 may decrease Erdafitinib plasma concentrations.

 

·   Decreased Erdafitinib plasma concentrations may lead to decreased activity.

Clinical management

·   If a moderate CYP2C9 or CYP3A4 inducer must be co-administered at the start of Balversa treatment, administer Balversa dose as recommended (8 mg once daily with potential to increase to 9 mg once daily based on serum phosphate levels on Days 14 to 21 and tolerability).

·   If a moderate CYP2C9 or CYP3A4 inducer must be co-administered after the initial dose increase period based on serum phosphate levels and tolerability, increase Balversa dose up to 9 mg.

·   When a moderate inducer of CYP2C9 or CYP3A4 is discontinued, continue Balversa at the same dose, in the absence of drug-related toxicity.

Serum Phosphate Level-

Altering Agents

 

Clinical Impact

·   Co-administration of Balversa with other serum phosphate level-altering agents may increase or decrease serum phosphate levels [see Pharmacodynamics (5.1)].

·   Changes in serum phosphate levels due to serum phosphate level-altering agents (other than Erdafitinib) may interfere with serum phosphate levels needed for the determination of initial dose increased based on serum phosphate levels.

Clinical management

·   Avoid co-administration of serum phosphate level-altering agents with Balversa before initial dose increase period based on serum phosphate levels (Days 14 to 21) [see Posology and method of Administration (4.2)].

 

 

Effect of Balversa on other drugs

 

CYP3A4 Substrates

Clinical Impact

·   Co-administration of Balversa with CYP3A4 substrates may alter the plasma concentrations of CYP3A4 substrates.

·   Altered plasma concentrations of CYP3A4 substrates may lead to loss of activity or increased toxicity of the CYP3A4 substrates.

Clinical management

·   Avoid co-administration of Balversa with sensitive substrates of CYP3A4 with narrow therapeutic indices.

OCT2 Substrates

Clinical Impact

·  Co-administration of Balversa with OCT2 substrates may increase the plasma concentrations of OCT2 substrates.

·  Increased plasma concentrations of OCT2 substrates may lead to increased toxicity of the OCT2 substrates.

Clinical management

·  Consider alternative therapies that are not OCT2 substrates or consider reducing the dose of OCT2 substrates (e.g., metformin) based on tolerability.

P-glycoprotein (P-gp) Substrates

Clinical Impact

·  Co-administration of Balversa with P-gp substrates may increase the plasma concentrations of P-gp substrates.

·  Increased plasma concentrations of P-gp substrates may lead to increased toxicity of the P-gp substrates.

Clinical management

If co-administration of Balversa with P-gp substrates is unavoidable, separate Balversa administration by at least 6 hours before or after administration of

P-gp substrates with narrow therapeutic index.


Pregnancy

 

There are no available data on Balversa use in pregnant women to inform a drug-associated risk. Based on the mechanism of action and findings in animal reproduction studies, Balversa can cause fetal harm when administered to a pregnant woman [see Pharmacological Properties (5)].

Oral administration of Erdafitinib to pregnant rats during organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum recommended human dose based on AUC.

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Lactation

There are no data on the presence of Erdafitinib in human milk, or the effects of Erdafitinib on the breastfed child, or on milk production.

Because of the potential for serious adverse reactions from Erdafitinib in a breastfed child, advise lactating women not to breastfeed during treatment with Balversa and for one month following the last dose.

 

Females and Males of Reproductive Potential

 

Pregnancy Testing

 

Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with Balversa.

 

Contraception

 

Females

Balversa can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with Balversa and for one month after the last dose.

 

Males

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Balversa and for one month after the last dose.

 

Infertility

 

Females

 

Based on findings from animal studies, Balversa may impair fertility in females of reproductive potential [see preclinical safety (5.3)].


Eye disorders such as central serous retinopathy or keratitis have been noted with FGFR inhibitors and with TRADENAME treatment. If patients experience treatment related symptoms affecting their vision, it is recommended that they do not drive or use machines until the effect subsides.


Summary of the safety profile

The most common adverse reactions (ARs) ≥15% were hyperphosphatemia, stomatitis, diarrhea, dry mouth, decreased appetite, dry skin, alopecia, palmar-plantar erythrodysesthesia syndrome, dry eye, onycholysis, paronychia,nail dystrophy and weight decreased. The most common G3 ARs >1% were stomatitis, hyponatremia,  nail dystrophy, palmar- plantar erythrodysesthesia syndrome, paronychia, nail disorder, keratitis, onycholysis, acute kidney injury and hyperphosphatemia. Adverse reactions leading to dose reduction occurred in patients, including for eye disorders. Patients experienced ARs leading to treatment discontinuation, including for eye disorders.

 

Below table presents ARs reported in ≥1% of patients treated with Balversa at 8 mg once daily in study BLC2001

Tabulated list of adverse reactions

The frequency categories of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000); not known (cannot be estimated from the available data). Following this definition, the adverse reaction categories reported in patients treated with Balversa in study BLC2001(N=99) were either very common (≥1/10) or common (≥1/100 to <1/10).

System Organ Class

Frequency of adverse reactions

 

Very common

(≥1/10)

Common

(≥1/100 to <1/10)

Uncommon

(≥1/1,000

to <1/100)

Rare

(≥1/10,000

to

<1/1,000)

Very rare (<1/10,000)

Not known

Metabolism and nutrition disorders

Hyperphosphatemia, Decreased Appetite

hyponatremia

 

 

 

 

 

Gastrointestinal disorders

Stomatitis,

Dry mouth Diarrhea

 

 

 

 

 

Skin and

subcutaneous tissue disorders

Dry skin,

Alopecia,

Nail disorder,

Onychomadesisi

 

 

 

 

 

Palmar-plantar erythrodysesthesia

syndrome,

Onychalgia,

Pruritus,

 

Onycholysis,

Skin fissures,

 

Paronychia

Nail ridging,

 

Nail dystrophy,

Onychoclasis,

 

Nail discoloration

Eczema,

 

 

Hyperkeratosis, Skin exfoliation, Skin lesion

Eye disorders

Dry eye,

Conjunctivitis

Chorioretinopathy,

Detachment of retinal pigment epithelium,

Keratitis,

Retinal detachment,

Retinal edema, Xerophthalmia, Retinopathy,

Ulcerative keratitis,

Vitreous detachment

Nervous system disorders

Dysgeusiaii

 

 Investigations

 Weight decreased,

 

Blood creatinine increased

 

Respiratory, thoracic and mediastinal disorders

 

Nasal dryness

Epistaxis

 

Renal and urinary disorders

 

Acute kidney injury

General disorders and administration site conditions

 

Mucosal dryness

 

Adverse events were coded using MedDRA version 20.0. In MedDRA version 20.0, the preferred terms of "Paronychia" and "Conjunctivitis" are coded to the system organ class of "Infections and infestations." In this analysis, they have been coded to the system organ classes of "Skin and subcutaneous tissue disorders" and "Eye disorders", respectively.

 

i Mod 2.5/ Section 5 (Clinical Overview, Update to the CCDS Regarding the Addition of Dysgeusia, Onychomadesis, Calciphylaxis and Cutaneous calcification as an Adverse Drug Reaction (ADR), EDMS-RIM-762621.

ii Mod 2.5/ Section 5 (Clinical Overview, Update to the CCDS Regarding the Addition of Dysgeusia, Onychomadesis,

Calciphylaxis and Cutaneous calcification as an Adverse Drug Reaction (ADR), EDMS-RIM-762621.

 

The following ARs were reported with the administration of BALVERSA in BLC2001 and other studies: Ocular Disorders

Balversa can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) resulting in visual field defect.

CSR/RPED was reported in 25% of patients treated with Balversa, with a median time to first onset of 50 days. Grade 3 CSR/RPED, involving central field of vision, was reported in 3% of patients. CSR/RPED resolved in 13% of patients and was ongoing in 13% of patients at the study cutoff. CSR/RPED led to dose interruptions and reductions in 9% and 14% of patients, respectively and 3% of patients discontinued Balversa.

Dry eye symptoms occurred in 28% of patients during treatment with Balversa and were Grade 3 in 6% of patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed.

Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms. Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography.

Withhold Balversa when CSR occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 in severity. For ocular adverse reactions, follow the dose modification guidelines [see Posology and method of administration (4.2) ].

 

 

Hyperphosphatemia

Increases in phosphate concentrations are an expected and transient laboratory abnormality. Hyperphosphatemia was reported as an adverse event in patients treated with Balversa. No event of hyperphosphatemia was reported as serious. The median onset time for any grade event of hyperphosphatemia was 20 days. Mean phosphate elevations peaked approximately 6 weeks after the start of Balversa and subsequently decreased to below 4.5 mg/dL by approximately month 5.

 

Electrolyte Abnormalities

In addition, the following electrolyte imbalances were reported;

calcium increased, phosphate decreased , sodium decreased, and magnesium decreased.

 

Elevated liver enzymes

An increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were reported.

 

Gastrointestinal disorders

Abdominal pain, nausea, constipation, and diarrhea were reported.

 

Others

Fatigue, dysgeusia, musculoskeletal pain, increased creatinine, decreased albumin, and decreased hemoglobin were reported.

 

Embryo-Fetal Toxicity

Based on the mechanism of action and findings in animal reproduction studies, Balversa can cause fetal harm when administered to a pregnant woman. In an embryo-fetal toxicity study, oral administration of erdafitinib to pregnant rats during the period of organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum human recommended dose based on area under the curve (AUC). Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with Balversa and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Balversa and for one month after the last dose [ Fertility, pregnancy and lactation (4.6) and Pharmacological Properties (5)].

 

To report any side effect(s):

Saudi Arabia:

 
 

 

·         The National Pharmacovigilance Centre (NPC):

-         SFDA Call Center: 19999

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

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

Other GCC States:

Please contact the relevant competent authority.

 

 


In the event of an overdose, stop BALVERSA, undertake general supportive measures until clinical toxicity has diminished or resolved.


1.1 Pharmacotherapeutic group: ATC code: L01EN01 Mechanism of Action

Erdafitinib is a kinase inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3 and FGFR4 based on in vitro data. Erdafitinib also binds to RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, and VEGFR2. Erdafitinib inhibited FGFR phosphorylation and signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions. Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer.

 

Pharmacodynamic effects

 

Cardiac Electrophysiology

Based on evaluation of QTc interval in an open-label, dose escalation and dose expansion study in 187 patients with cancer, Erdafitinib had no large effect (i.e., > 20 ms) on the QTc interval.

 

Serum Phosphate

 

Erdafitinib increased serum phosphate level as a consequence of FGFR inhibition. Balversa should be increased to the maximum recommended dose to achieve target serum phosphate levels of 5.5–7.0 mg/dL in early cycles with continuous daily dosing [see posology and method of administration (4.2)].

In Erdafitinib clinical trials, the use of drugs which can increase serum phosphate levels, such as potassium phosphate supplements, vitamin D supplements, antacids, phosphate-containing enemas or laxatives, and medications known to have phosphate as an excipient were prohibited unless no alternatives exist. To manage phosphate elevation, phosphate binders were permitted. Avoid concomitant use with agents that can alter serum phosphate levels before the initial dose increase period based on serum phosphate levels.

 

Clinical efficacy and safety

 

Urothelial Carcinoma with Susceptible FGFR Genetic Alterations

 

Study BLC2001 (NCT02365597) was a multicenter, open-label, single-arm study to evaluate the efficacy and safety of Balversa in patients with locally advanced or metastatic urothelial carcinoma (mUC).

Fibroblast growth factor receptor (FGFR) mutation status for screening and enrollment of patients was determined by a clinical trial assay (CTA). The efficacy population consists of a cohort of eighty-seven patients who were enrolled in this study with disease that had progressed on or after at least one prior chemotherapy and that had at least 1 of the following genetic alterations: FGFR3 gene mutations (R248C, S249C, G370C, Y373C) or FGFR gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1,

FGFR2-CASP7), as determined by the CTA performed at a central laboratory. Tumor samples from 69 patients were tested retrospectively by the QIAGEN therascreen® FGFR RGQ RT-PCR Kit, which is the FDA-approved test for selection of patients with mUC for BALVERSA.

 

Patients received a starting dose of BALVERSA at 8 mg once daily with a dose increase to 9 mg once daily in patients whose serum phosphate levels were below the target of 5.5 mg/dL between days 14 and 17; a dose increase occurred in 41% of patients.

 

Balversa was administered until disease progression or unacceptable toxicity. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR), as determined by blinded independent review committee (BIRC) according to RECIST v1.1.

 

The median age was 67 years (range: 36 to 87 years), 79% were male, and 74% were Caucasian. Most patients (92%) had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Sixty-six percent of patients had visceral metastases. Eighty-four (97%) patients received at least one of cisplatin or carboplatin previously. Fifty-six percent of patients only received prior cisplatin-based regimens, 29% received only prior carboplatin-based regimens, and 10% received both cisplatin and carboplatin-based regimens. Three (3%) patients had disease progression following prior platinum- containing neoadjuvant or adjuvant therapy only. Twenty-four percent of patients had been treated with prior anti PD-L1/PD-1 therapy. Overall response rate was 32.2%. Responders included patients who had previously not responded to anti PDL1/PD-1 therapy.


Following administration of 8 mg once daily, the mean (coefficient of variation [CV%]) erdafitinib steady-state maximum observed plasma concentration (Cmax), area under the curve (AUCtau), and minimum observed plasma concentration (Cmin) were 1,399 ng/mL (51%), 29,268 ng·h/mL (60%), and

936 ng/mL (65%), respectively.

 

Following single and repeat once daily dosing, erdafitinib exposure (maximum observed plasma concentration [Cmax] and area under the plasma concentration time curve [AUC]) increased proportionally across the dose range of 0.5 to 12 mg (0.06 to 1.3 times the maximum approved recommended dose). Steady state was achieved after 2 weeks with once daily dosing and the mean accumulation ratio was 4-fold.

 

Absorption

 

Median time to achieve peak plasma concentration (tmax) was 2.5 hours (range: 2 to 6 hours).

Effect of Food

No clinically meaningful differences with Erdafitinib pharmacokinetics were observed following administration of a high-fat and high-calorie meal (800 calories to 1,000 calories with approximately 50% of total caloric content of the meal from fat) in healthy subjects.

 

Distribution

 

The mean apparent volume of distribution of Erdafitinib was 29 L in patients.

Erdafitinib protein binding was 99.8% in patients, primarily to alpha-1-acid glycoprotein.

 

Elimination

The mean total apparent clearance (CL/F) of Erdafitinib was 0.362 L/h in patients. The mean effective half-life of Erdafitinib was 59 hours in patients.

 

Metabolism

 

Erdafitinib is primarily metabolized by CYP2C9 and CYP3A4. The contribution of

CYP2C9 and CYP3A4 in the total clearance of Erdafitinib is estimated to be 39% and 20% respectively. Unchanged Erdafitinib was the major drug-related moiety in plasma, there were no circulating metabolites.

 

Excretion

Following a single oral dose of radiolabeled Erdafitinib, approximately 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged).

 

Specific Populations

 

No clinically meaningful trends in the pharmacokinetics of Erdafitinib were observed based on age (21-88 years), sex, race, body weight (36-132 kg), mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, or mild to moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m²) .Limited data are available in patients with severe (Child-Pugh C) hepatic impairment.

 

The pharmacokinetics of erdafitinib in patients with severe renal impairment and renal impairment requiring dialysis is unknown.

 

Renal Impairment

 

No dose adjustment is recommended for patients with mild to moderate renal impairment [estimated glomerular filtration rate (eGFR) 30 to 89 mL/min/1.73 m²]. No data are available in patients with severe renal impairment.

 

Hepatic Impairment

No dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Limited data are available in patients with severe (Child-Pugh C) hepatic impairment.

 

CYP2C9 Poor Metabolizers

CYP2C9*3/*3 Genotype: Erdafitinib plasma concentrations were predicted to be higher in patients with the CYP2C9*3/*3 genotype. Monitor for increased adverse reactions in patients who are known or suspected to have CYP2C9*3/*3 genotype.


Carcinogenesis

Carcinogenicity studies have not been conducted with Erdafitinib.

Mutagenesis

Erdafitinib was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an

in vitro micronucleus or an in vivo rat bone marrow micronucleus assay.

Impairment of Fertility

Fertility studies in animals have not been conducted with Erdafitinib. In the 3-month repeat-dose toxicity study, Erdafitinib showed effects on female reproductive organs (necrosis of the ovarian corpora lutea) in rats at an exposure less than the human exposure (AUC) at maximum recommended human dose.

 


Tablet Core: Croscarmellose sodium, Magnesium stearate (from vegetable source), Mannitol, Meglumine, and Microcrystalline Cellulose.

 

Film Coating: (Opadry amb II): Glycerol monocaprylocaprate Type I, Polyvinyl alcoholpartially hydrolyzed, Sodium lauryl sulfate, Talc, Titanium dioxide, Iron oxide yellow,Iron oxide red (for the orange and brown tablets only), Ferrosoferric oxide/iron oxide black (for the brown tablets only).


Not applicable


3 years

Do not store above 30°C


For 3 mg tablets available in:

Bottle of 56-tablets with child resistant closure. Bottle of 84-tablets with child resistant closure.

 

For 4 mg tablets available in:

Bottle of 28-tablets with child resistant closure. Bottle of 56-tablets with child resistant closure.

 

For 5 mg tablets available in:

Bottle of 28-tablets with child resistant closure.

 

Balversa is available in a white 40 cc HDPE bottle with a child-resistant polypropylene closure and 2 x 1 g desiccant pouches.

Not all pack sizes may be marketed

 


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


Janssen Biotech inc 800 850 Ridgeview Drive Horsham United States

5 July 2023
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