nama bahan kemas leaflet docetaxel docetaxel ... docetaxel (2...nama obat ini adalah docetaxel...

Baca semua leaflet ini dengan seksama sebelum Anda mulai menggunakan obat ini karena mengandung informasi penting untuk Anda- Simpan leaflet ini. Anda mungkin perlu untuk membacanya lagi.- Jika Anda memiliki pertanyaan lebih lanjut, tanyakan kepada dokter, apoteker rumah sakit atau perawat Anda.- Jika Anda mendapatkan efek samping, bicarakan pada dokter, apoteker rumah sakit atau perawat Anda. Hal ini termasuk efek samping yang mungkin tidak tercantum dalam leaflet ini.

Apa yang ada di leaflet ini :1. Apa DOCETAXEL TRIHYDRATE dan apa kegunaannya2. Apa yang perlu Anda ketahui sebelum Anda menggunakan DOCETAXEL TRIHYDRATE3. Cara menggunakan DOCETAXEL TRIHYDRATE4. Kemungkinan efek samping5. Bagaimana untuk menyimpan DOCETAXEL TRIHYDRATE6. Isi dari kemasan dan informasi lainnya

1. APA DOCETAXEL TRIHYDRATE (DOCETAXEL) DAN APA KEGUNAANNYA Nama obat ini adalah DOCETAXEL TRIHYDRATE. Nama umumnya adalah docetaxel. Docetaxel adalah zat yang berasal dari jarum pohon yew. Docetaxel termasuk dalam kelompok obat anti-kanker yang disebut taksoid.

Kegunaan Docetaxel Trihydrate :- Kanker payudara DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan doxorubicin dan cyclophosphamide diindikasikan untuk pengobatan adjuvant untuk pasien dengan: • kanker payudara node-positif yang dapat dioperasi. • kanker payudara node-negatif yang dapat dioperasi.

Untuk pasien dengan kanker payudara node-negatif yang dapat dioperasi, pengobatan adjuvant harus dibatasi untuk pasien yang memenuhi syarat untuk menerima kemoterapi sesuai dengan kriteria yang telah ditetapkan secara internasional untuk terapi utama kanker payudara dini.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan doxorubicin diindikasikan untuk pengobatan pasien dengan kanker payudara stadium lanjut atau metastasis yang belum pernah menerima terapi sitotoksik untuk kondisi ini.

DOCETAXEL TRIHYDRATE (docetaxel) monoterapi diindikasikan untuk pengobatan pasien dengan kanker payudara stadium lanjut atau metastasis setelah kegagalan terapi sitotoksik. Kemoterapi sebelumnya harus telah menyertakan salah satu anthracycline atau zat alkilasi.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan trastuzumab diindikasikan untuk pengobatan pasien dengan kanker payudara metastasis dengan tumor yang diekspresikan berlebih HER2 dan yang sebelumnya belum menerima kemoterapi untuk penyakit metastasis.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan capecitabine diindikasikan untuk pengobatan pasien dengan stadium lanjut atau kanker payudara metastasis setelah gagal kemoterapi sitotoksik; Terapi sebelumnya harus telah menyertakan salah satu anthracycline.

- Kanker paru-paru non-sel kecil DOCETAXEL TRIHYDRATE (docetaxel) diindikasikan untuk pengobatan pasien kanker paru-paru non-sel kecil dengan stadium lanjut atau metastasis setelah gagal kemoterapi sebelumnya.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan cisplatin diindikasikan untuk pengobatan pasien dengan dioperasi, kanker paru-paru non-sel kecil lanjut secara lokal atau metastasis, pada pasien yang belum pernah menerima kemoterapi untuk kondisi ini.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan carboplatin merupakan pilihan pengobatan untuk terapi berbasis cisplatin.

- Kanker prostat DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan prednisone atau prednisolone diindikasikan untuk pengobatan pasien dengan kanker prostat metastasis hormon refraktori.

- Kanker lambung DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan cisplatin dan 5-fluorouracil diindikasikan untuk pengobatan pasien dengan kanker lambung metastasis, termasuk kanker pada gastroesophageal junction, yang belum menerima kemoterapi sebelumnya untuk penyakit metastasis.

- Kanker kepala dan leher DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan cisplatin dan 5-fluorouracil diindikasikan untuk induksi pengobatan pasien dengan kanker sel squamous lanjut secara lokal dari kepala dan leher

- Kanker rahim Docetaxel Trihydrate (docetaxel) diindikasikan untuk pengobatan pasien dengan kanker metastasis dari ovarium setelah kegagalan lini pertama atau kemoterapi berikutnya.2. APA YANG ANDA HARUS TAHU SEBELUM MENGGUNAKAN DOCETAXEL TRIHYDRATE Anda tidak boleh diberikan DOCETAXEL TRIHYDRATE jika • Anda alergi (hipersensitif) terhadap docetaxel atau bahan lain dari DOCETAXEL TRIHYDRATE. • Jumlah sel darah putih terlalu rendah. • Anda memiliki penyakit hati yang berat.

Peringatan dan tindakan pencegahanSebelum setiap pengobatan dengan DOCETAXEL TRIHYDRATE, Anda harus menjalani tes darah untuk memeriksa apakah Anda memiliki cukup sel darah dan fungsi hati yang cukup untuk menerima DOCETAXEL TRIHYDRATE. Dalam kasus gangguan sel darah putih, Anda mungkin mengalami demam atau infeksi yang berhubungan.Anda akan diminta untuk mengambil premedikasi yang terdiri dari kortikosteroid yang

Nama Bahan Kemas

Kode Bahan Kemas

Menggantikan Kode

Kode Pharmacode

Menggantikan Kode

FINAL ARTWORKLeaflet Docetaxel

0030

-

CKD01S0079

-

Keterangan Dasar

Ukuran : 380 x 350 mmBahan : HVS 60 g/m2

Warna : Hitam (cetak 2 muka / bolak-balik)

diminum seperti dexamethasone, satu hari sebelum pemberian DOCETAXEL TRIHYDRATE dan akan terus berlanjut selama satu atau dua hari setelah itu untuk meminimalkan efek tertentu yang tidak diinginkan yang mungkin terjadi setelah pemberian infus DOCETAXEL TRIHYDRATE dalam reaksi alergi dan retensi cairan tertentu (pembengkakan tangan, kaki atau peningkatan berat badan). Selama perawatan, Anda mungkin akan diberi obat-obatan lain untuk menjaga jumlah sel darah Anda. DOCETAXEL TRIHYDRATE mengandung alkohol. Diskusikan dengan dokter jika Anda menderita ketergantungan alkohol atau gangguan hati. Lihat juga bagian "DOCETAXEL TRIHYDRATE berisi etanol (alkohol)" di bawah ini.

Obat-obatan lain dan DOCETAXEL TRIHYDRATETolong beritahu dokter atau apoteker rumah sakit jika Anda menggunakan atau baru saja mengkonsumsi obat lain, termasuk obat-obatan yang diperoleh tanpa resep. Hal ini karena DOCETAXEL TRIHYDRATE atau obat lain tidak dapat bekerja dengan baik seperti yang diharapkan dan Anda akan lebih mungkin terkena efek samping.

Kehamilan, menyusui dan kesuburanMintalah dokter Anda untuk memberi saran sebelum diberikan obat apapun.DOCETAXEL TRIHYDRATE TIDAK boleh diberikan jika Anda sedang hamil kecuali dengan jelas ditunjukkan oleh dokter Anda.Anda tidak boleh hamil selama pengobatan dengan obat ini dan harus menggunakan metode kontrasepsi yang efektif selama terapi, karena DOCETAXEL TRIHYDRATE mungkin berbahaya bagi bayi yang belum lahir. Jika kehamilan terjadi selama pengobatan Anda, Anda harus segera memberitahu dokter Anda. Anda tidak boleh menyusui saat Anda menerima pengobatan dengan dengan DOCETAXEL TRIHYDRATE.Jika Anda seorang pria yang dirawat dengan DOCETAXEL TRIHYDRATE Anda disarankan untuk tidak punya anak selama dan sampai 6 bulan setelah pengobatan dan mencari rekomendasi untuk konservasi sperma sebelum perawatan karena docetaxel dapat mengu-bah kesuburan pria.

Mengemudi dan menggunakan mesinTidak ada studi tentang efek pada kemampuan mengemudi dan menggunakan mesin yang telah dilakukan.

DOCETAXEL TRIHYDRATE mengandung etanol (alkohol)Produk obat ini mengandung 0.42 ml etanol (alkohol) setiap ml vialnya.Berbahaya bagi mereka yang menderita alkoholisme.Untuk dipertimbangkan jika Anda wanita hamil atau jika Anda sedang menyusui, anak-anak dan kelompok berisiko tinggi seperti pasien dengan penyakit hati, atau epilepsi.Jumlah alkohol dalam produk obat dapat mengubah efek obat lain.Jumlah alkohol dalam obat ini dapat mengganggu kemampuan Anda mengemudi atau menggunakan mesin.

3. BAGAIMANA MENGGUNAKAN DOCETAXEL TRIHYDRATEDOCETAXEL TRIHYDRATE akan diberikan kepada Anda oleh seorang tenaga kesehatan.

Dosis pada umumnyaDosisnya akan tergantung pada berat badan dan kondisi umum Anda. Dokter Anda akan menghitung luas permukaan tubuh Anda dalam meter persegi (m2) dan akan menentukan dosis yang harus Anda terima.

Metode dan rute pemberianDOCETAXEL TRIHYDRATE akan diberikan melalui infus ke dalam salah satu pembuluh darah Anda (rute IV). Infus akan berlangsung sekitar satu jam selama Anda dirawat di rumah sakit.

Frekuensi pemberianAnda biasanya harus menerima infus Anda sekali setiap 3 minggu.

Dokter Anda dapat mengubah dosis dan frekuensi dosis tergantung pada tes darah, kondisi umum dan respons Anda terhadap DOCETAXEL TRIHYDRATE. Secara khusus, silahkan beritahu dokter Anda jika terjadi diare, luka di mulut, berasa baal atau kesemutan, demam dan berikan hasil tes darah kepada dokter Anda. Informasi tersebut akan memungkinkan dokter Anda untuk memutuskan apakah pengurangan dosis diperlukan. Jika Anda memiliki pertanyaan lebih lanjut pada penggunaan obat ini, tanyakan kepada dokter atau apoteker rumah sakit Anda.

4. KEMUNGKINAN EFEK SAMPINGSeperti obat-obatan lainnya, obat ini dapat menyebabkan efek samping, meskipun tidak semua orang merasakannya.

Dokter Anda akan membicarakan hal ini kepada Anda dan akan menjelaskan potensi risiko dan manfaat dari perawatan Anda.Reaksi yang paling sering dilaporkan dari penggunaan DOCETAXEL TRIHYDRATE tunggal adalah: penurunan jumlah sel darah merah atau sel darah putih, kerontokan rambut, mual, muntah, luka pada mulut, diare, dan kelelahan.Tingkat keparahan efek samping dari DOCETAXEL TRIHYDRATE dapat meningkat ketika DOCETAXEL TRIHYDRATE diberikan dalam kombinasi dengan agen kemoterapi lain.

Selama infus di rumah sakit reaksi alergi berikut (dapat terjadi lebih dari 1 dari 10 orang) :• wajah terasa panas, reaksi kulit, gatal• dada sesak, kesulitan bernafas• demam atau kedinginan• sakit punggung• tekanan darah rendah

Reaksi yang lebih parah dapat terjadi.

Staf rumah sakit akan memantau kondisi Anda dengan erat selama pengobatan. Katakan kepada mereka segera jika Anda melihat salah satu dari efek ini.

Antara infus DOCETAXEL TRIHYDRATE, yang berikut ini dapat terjadi, dan frekuensinya mungkin berbeda dengan kombinasi obat-obatan yang diterima:Sangat umum (dapat terjadi lebih dari 1 dari 10 orang) :• infeksi, penurunan jumlah sel darah merah (anemia), atau sel darah putih (yang penting dalam melawan infeksi) dan trombosit• demam: jika terjadi demam, Anda harus memberitahu dokter Anda segera• reaksi alergi seperti dijelaskan di atas• hilangnya nafsu makan (anoreksia)• kesulitan untuk tidur• perasaan baal atau kesemutan atau nyeri pada sendi atau otot• sakit kepala• perubahan pada indera perasa• radang mata atau melimpahnya air mata• pembengkakan yang disebabkan oleh gangguan aliran limfa• sesak napas• gangguan aliran pada hidung; radang pada tenggorokan dan hidung; batuk

• perdarahan dari hidung• luka di mulut• gangguan pada perut seperti mual, muntah dan diare, sembelit• nyeri pada perut• gangguan pencernaan• rambut rontok (dalam banyak kasus pertumbuhan rambut normal akan kembali)• kemerahan dan pembengkakan pada telapak tangan atau telapak kaki Anda yang dapat menyebabkan kulit Anda mengelupas (ini juga dapat terjadi pada lengan, wajah, atau tubuh)• perubahan warna kuku, yang mungkin akan terlepas• Sakit pada otot dan nyeri, sakit punggung atau nyeri tulang• perubahan atau tidak adanya menstruasi• pembengkakan tangan, kaki, betis• kelelahan, atau gejaia seperti flu• bertambah atau berkurangnya berat badan.

Umum (dapat terjadi lebih dari 1 dari 10 orang) :• kandidiasis (infeksi jamur yang disebabkan oleh jamur Candida albicans) pada mulut• dehidrasi• pusing• hilangnya fungsi pendengaran• penurunan tekanan darah, detak jantung yang tidak teratur atau cepat• gagal jantung• radang pada esophagus• mulut kering• kesulitan atau sakit saat menelan• perdarahan• peningkatan enzim hati (maka dibutuhkan untuk tes darah secara rutin)

Tidak umum (dapat terjadi lebih dari 1 dari 100 orang) :• pingsan• pada tempat suntikan: reaksi kulit, flebitis (radang pembuluh darah) atau pembengkakan• radang usus, usus kecil, perforasi usus• pembekuan darah

Frekuensi tidak diketahui :• Penyakit paru interstisial (radang paru-paru menyebabkan batuk dan sulit bernafas, peradangan paru-paru juga bisa berkembang saat terapi doksetasel digunakan dengan radioterapi)• Pneumonia (infeksi paru-paru)• Fibrosis paru (jaringan parut dan penebalan paru-paru dengan sesak napas)• Penglihatan kabur akibat pembengkakan retina di mata (cystoid macular edema)• Penurunan natrium, kalium, magnesium dan / atau kalsium dalam darah anda (gangguan keseimbangan elektrolit)• Ventrikel aritmia atau ventrikel takikardia (manifestasi sebagai detak jantung yang tidak teratur dan / atau cepat, sesak napas hebat, pusing, dan / atau pingsan). Beberapa gejala ini bisa serius. Jika ini terjadi, segera beri tahu dokter anda• Reaksi di tempat suntikan di tempat reaksi sebelumnya.

Jika Anda mengalami efek samping beri tahukan dokter, apoteker rumah sakit atau perawatAnda. Hal ini termasuk efek samping yang mungkin tidak tercantum dalam leaflet ini.

5. BAGAIMANA MENYIMPAN DOCETAXEL TRIHYDRATEJauhkan obat ini dari pandangan dan jangkauan anak-anak.Obat ini tidak boleh digunakan setelah tanggal kadaluwarsa yang tercantum pada kotak dan label vial setelah kadaluwarsa, tanggal kadaluwarsa mengacu pada tanggal terakhir bulan tersebut.Jangan simpan pada suhu di atas 30°C.Simpan dalam kemasan asli untuk melindungi dari cahaya.Gunakan botol segera setelah pembukaannya. Jika tidak langsung digunakan, waktupenyimpanan dalam penggunaan dan kondisi adalah tanggung jawab pengguna.Dari sudut pandang mikrobiologi, rekonstitusi / pengenceran harus berlangsung dalam kondisi yang terkendali dan aseptik.Gunakan obat segera setelah ditambahkan ke dalam kantong infus. Jika tidak langsung digunakan, waktu penyimpanan dalam penggunaan dan kondisi adalah tanggung jawab pengguna dan biasanya tidak lebih lama dari 6 jam pada suhu di bawah 30°C termasuk infus satu jam.Larutan infus Docetaxel bersifat jenuh, karena itu mungkin mengkristal dari waktu ke waktu. Jika muncul kristal, larutan tersebut tidak boleh digunakan dan harus dibuang.Jangan membuang obat-obatan melalui air limbah. Tanyakan apoteker Anda bagaimana untuk membuang obat-obatan Anda tidak lagi digunakan. Langkah-langkah ini akan membantu melindungi lingkungan.

6. ISI KEMASAN DAN INFORMASI LAIN Apa isi DOCETAXEL TRIHYDRATE- Zat aktifnya adalah docetaxel (sebagai trihidrat). Setiap ml larutan konsentrat untuk infus mengandung 20 mg docetaxel.- Bahan-bahan lainnya adalah polisorbat 80, etanol anhidrat dan asam sitrat anhidrat.

Bagaimana rupa DOCETAXEL TRIHYDRATE dan isi kemasanLarutan konsentrat DOCETAXEL TRIHYDRATE untuk infus adalah larutan kuning sampai coklat kuning. • Docetaxel Trihydrate 20 mg/1 mL Konsentrat ini tersedia dalam vial gelas bening tidak berwarna berukuran 6 ml dengan segel karet dan flip-off alumunium berwarna hijau yang terhubung dengan tutup polipropilen. Setiap kotak berisi 1 vial 1 ml konsentrat (20 mg docetaxel).• Docetaxel Trihydrate 80 mg/4 mL Konsentrat ini tersedia dalam vial gelas bening tidak berwarna berukuran 6 ml dengan segel karet dan flip-off alumunium berwarna merah yang terhubung dengan tutup polipropilen. Setiap kotak berisi 1 vial 4 ml konsentrat (80 mg docetaxel).

Produsen :PT CKD OTTO PharmaceuticalsBekasi - Indonesia

Diregistrasikan oleh : PT CKD OTTO PharmaceuticalsBekasi - Indonesia

Peringatan : Cytotoxic Agent

DOCETAXEL TRIHYDRATE20 mg/1 mL & 80 mg/4 mL

Larutan Konsentrat untuk Infus

CKD

01S0

079

For packaging vendor1 / 2


Concentrate for Solution for Infusion

Warning : Cytotoxic Agent

COMPOSITION :Docetaxel Trihydrate 20 mg/1 mLEach mL of concentrate contains 20 mg Docetaxel as Trihydrate. One vial of 1 mL of concentrate contains 20 mg of Docetaxel and Ethanol 0.42 mL.Docetaxel Trihydrate 80 mg/4 mLEach mL of concentrate contains 20 mg Docetaxel as Trihydrate. One vial of 4 mL of concentrate contains 80 mg of Docetaxel and Ethanol 0.42 mL.PHARMACEUTICAL FORM :Concentrate for solution for infusion (sterile concentrate).The concentrate is a pale yellow to brownish-yellow solution.MECHANISM OF ACTION :PharmacologyDocetaxel is an antineoplastic agents which acts by promoting the assembly of tubulin into stable microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The binding of Docetaxel to microtubules does not alter the number of protofilaments.Docetaxel is schedule independent and has a broad spectrum of experimental antitumour activity against advanced murine and human grafted tumours.INDICATION :Breast Cancer• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Doxorubicin and Cyclophosphamide is indicated for the adjuvant treatment of patients with : o operable node-positive breast cancer o operable node-negative breast cancer• For patients with operable node negative breast cancer, adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition.• DOCETAXEL TRIHYDRATE (Docetaxel) monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an Anthracycline or an alkylating agent.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumors over express HER2 and who previously have not received chemotherapy for metastatic disease.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Capecitabine indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an Anthracycline.Non Small Cell Lung Cancer• DOCETAXEL TRIHYDRATE (Docetaxel) is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not previously received chemotherapy for this condition.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Carboplatin represents a treatment option to Cisplatin based therapy.Prostate CancerDOCETAXEL TRIHYDRATE (Docetaxel) in combination with Prednison or Prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer.Gastric AdenocarcinomaDOCETAXEL TRIHYDRATE (Docetaxel) in combination with Cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease.Head and neck cancerDOCETAXEL TRIHYDRATE (Docetaxel) in combination with Cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.Ovarian cancerDOCETAXEL TRIHYDRATE (Docetaxel) is indicated for the treatment of patients with metastatic carcinoma of the ovary after failure of first line or subsequent chemotherapy.CONTRAINDICATION :• Hypersensitivity reactions to the active substance or to any of the excipients.• Patients with baseline neutrophil count of < 1,500 cells/mm3.• Patients with severe liver impairment (see “Special warnings and special precautions for use” and “Posology and method of and method of administration sections”).• Contraindications for other medicinal products also apply when combined with Docetaxel.ADVERSE REACTION :The most commonly adverse reaction was neutropenia, which was reversible and not cumulative. The median day to nadir was 7 days and the median duration of severe neutropenia (< 500 cells/mm3) was 7 days, anemia, alopecia, nausea, vomiting, stomatitis, diarrhoea and asthenia. The severity of adverse events of Docetaxel may be increased when Docetaxel is given in combination with other chemotherapeutic agents.The following adverse reactions are frequently observed with Docetaxel :Immune system disorders :Hypersensitivity reactions have generally occurred within a few minutes following the start of the infusion of Docetaxel and were usually mild to moderate. The most frequently reported symptoms were flushing, rash with or without pruritus, chest tightness, back pain, dyspnea and fever or chills. Severe reactions were characterized by hypotension and / or bronchospasm or generalized rash / erythema (see “Special warnings and precautions for use”).Nervous system disorders :The development of severe peripheral neurotoxicity requires a reduction of dose (see “Posology and method of administration” and “Special warnings and precautions for use”). Mild to moderate, neuro-sensory signs are characterized by paresthesia, dysesthesia or pain including burning. Neuro-motor events are mainly characterized by weakness.Skin and subcutaneous tissue disorders :Reversible cutaneous reaction have been observed and were generally considered as mild to moderate. Reactions were characterized by rash including localized eruption mainly on the feet and hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently associated with pruritus. Eruptions generally occurred within one week after the Docetaxel infusion. Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to interruption or discontinuation of Docetaxel treatment were reported (see “Posology and method of administration” and “Special warnings and precautions for use”). Severe nail disorders are characterized by hypo- or hyperpigmentation and sometimes pain and onycholysis.General disorders and administration site conditions :Infusion site reactions were generally mild and consisted of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis or extravasation and swelling of the vein.Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower extremities and may become generalized with a weight gain of 3 kg or more. Fluid retention is cumulative in incidence and severity (see “Special warnings and precautions for use”).Docetaxel 100 mg/m2 as a single agent :

Blood and lymphatic system disorders :Bleeding episodes accompanied by thrombocytopenia.Nervous system disorders :The data show a state of reversible occurred in patients who developed neurotoxicity following Docetaxel treatment at 100 mg/m2 as a single agent. These event spontaneously reversible within 3 months.Skin and subcutaneous tissue disorders :One case of alopecia non reversible at the end of the study. Cutaneous reactions were reversible within 21 days.Docetaxel 75 mg/m2 as a single agent :

Docetaxel 75 mg/m2 combination with Doxorubicin :

Docetaxel 75 mg/m2 combination with Cisplatin :

Docetaxel 100 mg/m2 combination with Trastuzumab :

Blood and lymphatic system disorders :Increased haematological toxicity in patients receiving Trastuzumab and Docetaxel compared with Docetaxel single. It should be noted that the situation was likely not taken into account because Docetaxel single dose of 100 mg/m2 is known to cause neutropenia in patients. The incidence of febrile neutropenia / neutropenic sepsis was also increased in patients treated with Trastuzumab plus Docetaxel.Cardiac disorders :Symptomatic heart failure have been reported in patients receiving Docetaxel plus Trastuzumab compared with patients given a single Docetaxel.Docetaxel 75 mg/m2 combination with Capecitabine :

Docetaxel 75 mg/m2 combination with Prednisone or Prednisolone :

Docetaxel 75 mg/m2 combination with Doxorubicin and Cyclophosphamide :

Docetaxel 75 mg/m2 combination with Cisplatin and 5-fluorouracil for gastric adenocarcinoma cancer :

Docetaxel 75 mg/m2 combination with Cisplatin and 5-fluorouracil for head and neck cancer :

SPECIAL WARNING AND SPECIAL PRECAUTIONS FOR USE :For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as Dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to Docetaxel administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral Dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the Docetaxel infusion (see “Posology and method of administrations”).HaematologyNeutropenia is the most frequent adverse reaction of Docetaxel. Neutrophil nadirs occurred at a median of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of complete blood counts should be conducted on all patients receiving Docetaxel. Patients should be retreated with Docetaxel when neutrophils recover to a level ≥ 1,500 cells/mm3 (see “Posology and method of administrations”).In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of Docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use appropriate symptomatic measures or recommended (see “Posology and method of administrations”).In patients treated with Docetaxel in combination with Cisplatin and 5-fluorouracil (TCF), febrile neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patient receiving TCF should be closely monitored (see “Posology and method of administrations” and “Adverse Reaction”).In patients treated with Docetaxel in combination with Doxorubicin and Cyclophosphamide (TAC), febrile neutropenia

and / or neutropenic infection occurred at lower rates when patients received primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be closely monitored (see “Posology and method of administrations” and “Adverse Reaction”).Gastrointestinal reactionsCaution is recommended for patients with neutropenia, particularly at risk for developing gastrointestinal complications. Enterocolitis could develop at any time, and could lead to death as early as on the first day of onset. Patients should be closely monitored for early manifestations of serious gastrointestinal toxicity (see sections Dosage and administration, Precaution - Haematology, Undesirable effect).Hypersensitivity reactionsPatients should be observed closely for hypersensitivity reactions especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of Docetaxel, thus facilities for the treatment of hypotension and bronchospasm should be available. If hypersensitivity reaction occur, minor symptoms such as flushing or localized cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe hypotension, bronchospasm or generalised rash / erythema require immediate discontinuation of Docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions should not be re-challenged with Docetaxel.Patients who have previously experienced a hypersensitivity reaction to Paclitaxel may be at risk to develop hypersensitivity to Docetaxel, including more severe hypersensitivity reaction. These patients should be closely monitored during initiation of Docetaxel therapy.Cutaneous reactionsLocalized skin erythema of the extremities (palms of the hands and soles of the feet) with oedema followed by desquamation has been observed. Severe symptoms such as eruptions followed by desquamation which lead to interruption or discontinuation of Docetaxel treatment were reported (see “Posology and method of administrations”).Fluid retentionPatients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be monitored closely.Patients with liver impairmentIn patients treated with Docetaxel at 100 mg/m2 as single agent who have serum transaminase levels (ALT and / or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia.Therefore, the recommended dose of Docetaxel in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at baseline and before each cycle (see “Posology and method of administrations”).For patients with serum bilirubin levels > ULN and / or ALT and AST > 3.5 times the ULN concurrent with serum alkaline phosphatase levels > 6 times the ULN. No dose-reduction can be recommended and Docetaxel should not be used unless strictly indicated.In combination with Cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical trial excluded patients with ALT and / or AST > 1.5 x ULN associated with alkaline phosphatase > 2.5 x ULN, and bilirubin > 1 x ULN; for these patients, no dose-reductions can be recommended and Docetaxel should not be used unless strictly indicated.No data are available in patients with hepatic impairment treated by Docetaxel in combination in the other indications.Patients with renal impairmentThere are no data available in patients with severely impaired renal function treated with Docetaxel.Nervous systemThe development of severe peripheral neurotoxicity requires a reduction of dose (see “Posology and method of administrations”).Cardiac toxicityHeart failure has been observed in patients receiving Docetaxel in combination with Trastuzumab, particularly following Anthracycline (Doxorubicin or Epirubicin) - containing chemotherapy. This may be moderate to severe and has been associated with death (see “Adverse Reaction”).When patients are candidates for treatment with Docetaxel in combination with Trastuzumab, they should undergo baseline cardiac assesment. Cardiac function should be further monitored during treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For more details see Summary of Product Characteristics of Trastuzumab.Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in patients treated with Docetaxel in combination regimens including Doxorubicin, 5-fluorouracil and / or Cyclophosphamide (see Section Undesirable Effect). Baseline cardiac assesstment is recommended.Eye disordersCystoid macular oedema (CMO) has been reported in patients treated with Docetaxel, as well as with other taxanes. Patients with impaired vision should undergo a prompt and complete opthalmogic examination. In case CMO is diagnosed, Docetaxel treatment should be discontinued and appropriate treatment initiated (see “Undesirable Effect”).OthersContraceptive measures must be taken by both men and women during treatment and for men at least 6 months after cessation of therapy (see “Pregnancy and Lactation”).The concomitant use of DOCETAXEL TRIHYDRATE with strong CYP3A4 inhibitors (e.g. Ketoconazole, Itraconazole, Clarithromycin, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin and Voriconazole) should be avoided (see “Interaction with other medicinal products and other forms of interaction”).Additional cautions for use in adjuvant treatment of breast cancerComplicated neutropeniaFor patients who experience complicated neutropenia (prolonged neutropenia, febrile neutopenia or infection), G-CSF and dose reduction should be considered (see “Posology and method of administration”).Gastrointestinal reactionsSymptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly.Congestive heart failurePatients should be monitored for symptoms of congestive heart failure during therapy and during the follow up period.LeukaemiaIn the Docetaxel, Doxorubicin and Cyclophosphamide (TAC) treated patients, the risk of delayed myelodysplasia or myeloid leukemia requires haematological follow up.Patients with 4+ nodesThe benefit / risk ratio for TAC in patients with 4+ nodes was not defined fully at the interim analysis.ElderlyThere are no data available in patients > 70 years of age on Docetaxel use in combination with Doxorubicin and Cyclophosphamide.ExcipientsThe amount of ethanol in DOCETAXEL TRIHYDRATE may be harmful in patients suffering from alcoholism and should also be taken into account in pregnant or breast-feeding women, in children and in high-risk groups such as patients with liver disease or epilepsy.Consideration should be given to possible effects on the central nervous system.The amount of ethanol in DOCETAXEL TRIHYDRATE may alter the effects of other medicinal products.The amount of ethanol in DOCETAXEL TRIHYDRATE may impair the ability to drive or use machines (see “Effects on ability to drive and use machines”).Interaction with other medicinal products and other forms of interactionIn vitro studies have shown that the metabolism of Docetaxel may be modified by the concomitant administration of compounds which induce, inhibit or are metabolized by (and thus may inhibit the enzyme competitively) cytochrome P450-3A such as Cyclosporine, Terfenadine, Ketoconazole, Erythromycin and Troleandomycin. As a result, caution should be exercised when treating patients with these medicinal products as concomitant therapy since there is a potential for a significant interaction.In case of combination with CYP3A4 inhibitors, the occurance of DOCETAXEL TRIHYDRATE adverse reactions may increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitors (e.g. Ketoconazole, Itraconazole, Clarithromycin, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin and Voriconazole) cannot be avoided, a close clinical surveillance is warranted and a dose-adjustment of DOCETAXEL TRIHYDRATE (Docetaxel) may be suitable during the treatment with the strong CYP3A4 inhibitor (see Special warnings and precautions for use). In a pharmacokinetic study with 7 patients, the co-administration of Docetaxel with the strong CYP3A4 inhibitor Ketoconazole leads to a significant decrease in Docetaxel clearance by 49%. Docetaxel pharmacokinetics in the presence of Prednisone was studied in patients with metastatic prostate cancer. Docetaxel is metabolized by CYP3A4 and Prednisone is known to induce CYP3A4. No statistically significant effect of Prednisone on the pharmacokinetics of Docetaxel was observed.Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of Docetaxel with concomitantly administered medication has not been investigated formally, in vitro interactions with tightly protein - bound agents such as Erythromycin, Diphenhydramine, Propanolol, Propafenone, Phenytoin, Salicylate, Sulfamethoxazole and Sodium Valproate did not affect protein binding of Docetaxel. In addition, Dexamethasone did not affect protein binding of Docetaxel. Docetaxel did not influence the binding of Digitoxin.The pharmacokinetics of Docetaxel, Doxorubicin and Cyclophosphamide were not influenced by their co-administration. Limited data from a single uncontrolled study were suggestive of an interaction between Docetaxel and Carboplatin. When combined to Docetaxel, the clearance of Carboplatin was about 50% higher than values previously reported for Carboplatin monotherapy.Clinical cases consistent with an increase in Docetaxel toxicity were reported when it was combined with Ritonavir. The mechanism behind this interaction is a CYP3A4 inhibition, the main isoenzyme involved in Docetaxel metabolism by Ritonavir. Based on extrapolation from a pharmacokinetic study with Ketoconazole in 7 patients, consider a 50% Docetaxel dose reduction if patients require co-administration of a strong CYP3A4 inhibitor such as azole antifungals, Ritonavir and some macrolides (Clarithromycin, Telithromycin).PREGNANCY AND LACTATION :There is no information on the use of Docetaxel in pregnant women. Docetaxel has been shown to be both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other cytotoxic medicinal products, Docetaxel may cause foetal harm when administered to pregnant women. Therefore, Docetaxel must not be used during pregnancy unless clearly indicated.Women of childbearing potential / contraceptionWomen of childbearing age receiving Docetaxel should be advised to avoid becoming pregnant and to inform the treating physician immediately should this occur.An effective method of contraception should be used during treatment.In non clinical studies, Docetaxel has genotoxic effects and may alter male fertility. Therefore, men being treated with Docetaxel are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment.LactationDocetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be discontinued for the duration of Docetaxel therapy.Effects on ability to drive and use machinesNo studies on the effects on the ability to drive and use machines have been performed.The amount of ethanol in DOCETAXEL TRIHYDRATE and the side effects of the product may impair the stability to drive or use machines (see section Special warning and Undesirable effect).Therefore, patients should be warned of the potential impact of the side effects of the product on the ability to drive or use machines, and be advised not to drive or use machines if they experiences these side effects during treatment.POSOLOGY AND METHOD OF ADMINISTRATIONS :The use of Docetaxel should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a physician qualified in the use of anticancer chemotherapy (see “Special Precautions for disposal and other handling”).Recommended dose :For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral corticosteroid, such as Dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to Docetaxel administration, unless contraindicated, can be used (see “Special warnings and precautions for use”). Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities.For prostate cancer, given the concurrent use of Prednisone or Prednisolone the recommended premedication regimen is oral Dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the Docetaxel infusion (see “Special warnings and precautions for use”).Docetaxel is administered as one - hour infusion every three weeks.Breast cancerIn the adjuvant treatment of operable node - positive and node - negative breast cancer, the recommended dose of Docetaxel is 75 mg/m2 administered 1-hour after Doxorubicin 50 mg/m2 and Cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustment during treatment).For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of Docetaxel is 100 mg/m2 in monotherapy. In the first line treatment, Docetaxel 75 mg/m2 is given in combination therapy with Doxorubicin (50 mg/m2).In combination with Trastuzumab the recommended dose of Docetaxel is 100 mg/m2 every three weeks, with Trastuzumab administered weekly. In the pivotal trial the initial Docetaxel infusion was started the day following the first dose of Trastuzumab. The subsequent Docetaxel doses were administered immediately after completion of the Trastuzumab infusion, if the preceding dose of Trastuzumab was well tolerated. For Trastuzumab dose and administration, see summary of product characteristics.

In combination with Capecitabine, the recommended dose of Docetaxel is 75 mg/m2 every 3 weeks, combine with Capecitabine at 1,250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks followed by 1-week rest period. For Capecitabine dose calculation according to body surface area, see Capecitabine summary of product characteristics.Non-small cell lung cancerIn chemotherapy naive patients treated for non-small cell lung cancer, the recommended dose regimen is Docetaxel 75 mg/m2 immediately followed by Cisplatin 75 mg/m2 over 30 - 60 minutes. For treatment after failure of prior platinum - based chemotherapy, the recommended dose is 75 mg/m2 as a single agent.Prostate cancerThe recommended dose of Docetaxel is 75 mg/m2. Prednisone or Prednisolone 5 mg orally twice daily is administered continuously.Gastric adenocarcinomaThe recommended dose of Docetaxel is 75 mg/m2 as a 1 hour infusion, followed by Cisplatin 75 mg/m2, as a 1 to 3 hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per day given as a 24-hours continuous infusion for 5 days, starting at the end of the Cisplatin infusion.Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for Cisplatin administration. Prophylactic G-CSF should be used to mitigate the risk of hematological toxicities (see also “Dose adjustment during treatment”).Head and neck cancerPatients must receive premedication with antiemetics and appropriate hydration (prior to and after Cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. All patients on the Docetaxel - containing arm of the studies, received prophylactic antibiotics.• Induction chemotherapy followed by radiotherapy (TAX 323) For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of Docetaxel is 75 mg/m2 as a 1 hour infusion followed by Cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.• Induction chemotherapy followed by chemoradiotherapy (TAX 324) For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of Docetaxel is 75 mg/m2 as 1 hour intravenous infusion on day 1, followed by Cisplatin 100 mg/m2 administered as a 30 minutes to 3 hours infusion, followed by 5-fluorouracil 1,000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.For Cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics.Ovarian cancerThe recommended dose of DOCETAXEL TRIHYDRATE (Docetaxel) is 75 to 100 mg/m2 administered as one - hour infusion every three weeks. A dose of 100 mg/m2 has been show to result in a moderate increase in response rates compared with 75 mg/m2 but is associated with greater toxicity.DOSE ADJUSTMENT DURING TREATMENT :GeneralDocetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm3. In patients who experienced either febrile neutropenia, neutrophil < 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during Docetaxel therapy, the dose of Docetaxel should be reduced from 100 mg/m2 to 75 mg/m2, and / or from 75 mg/m2 to 60 mg/m2. If the patient continues to experience there reactions at 60 mg/m2 the treatment should be discontinued.Adjuvant therapy for breast cancer :Primary G-CSF prophylaxis should be considered in patients who receive Docetaxel, Doxorubicin and Cylophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile neutropenia and / or neutropenic infection should have their docetaxel dose reduced to 60 mg/m2 in all subsequent cycles (see “Special warnings and precautions for use” and “Adverse Reaction”). Patient who experience Grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m2.However in clinical practice neutropenia could occur earlier. Thus the use of G-CSF should be considered function of the neutropenic risk of the patient and current recommendations. Patient who experience grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m2.In combination with cisplatin :For patients who are dosed initially at Docetaxel 75 mg/m2 in combination with Cisplatin and whose nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who experience febrile neutropenia, or in patients with serious non-hematologic toxicities, the Docetaxel dose in subsequent cycles should be reduced to 65 mg/m2. For Cisplatin dose adjustment, see the corresponding summary of product characteristics.In combination with Capecitabine :• For Capecitabine dose modification, see Capecitabine summary of product characteristics.• For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the next Docetaxel / Capecitabine treatment, delay treatment until resolved to Grade 0 - 1 and resume at 100% of the original dose.• For patients developing the second appearance of Grade 2 toxicity, or the first appearance of Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0 - 1 and then resume treatment with Docetaxel 55 mg/m2.• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the Docetaxel dose.• For Trastuzumab dose modifications, see Trastuzumab summary of product characteristics.In combination with Cisplatin and 5-fluorouracil :If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the Docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the Docetaxel dose should be reduced from 60 to 45 mg/m2. In case of Grade 4 thrombocytopenia the Docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should not be retreated with subsequent cycles of Docetaxel until neutrophils recover to a level > 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3. Discontinue treatment if these toxicities persist (see “Special warnings and precautions for use”).Recommended dose modifications for toxicities in patients treated with Docetaxel in combination with Cisplatin and 5-fluorouracil (5-FU).

For Cisplatin and 5-fluorouracil dose adjustment, see the corresponding summary of product characteristics.In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (e.g. day 6 - 15) in all subsequent cycles.SPECIAL POPULATION :Patients with hepatic impairmentBased on pharmacokinetic data with Docetaxel at 100 mg/m2 as single agent, patients who have both elevations of transaminase (ALT and / or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of Docetaxel is 75 mg/m2 (see “Special warnings and precautions for use”). For those patients with serum bilirubin > ULN and / or ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose-reduction can be recommended and Docetaxel should not be used unless strictly indicated.In combination with Cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical trial excluded patients with ALT and / or AST > 1.5 x ULN associated with alkaline phosphatase > 2.5 x ULN, and bilirubin > 1 x ULN; for these patients, no dose - reduction can be recommended and Docetaxel should not be used unless strictly indicated. No data are available in patients with hepatic impairment treated by Docetaxel in combination in the other indications.Pediatric populationDOCETAXEL TRIHYDRATE (Docetaxel) is not recommended for children.ElderlyBased on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. In combination with Capecitabine, for patients 60 years of age or more, a starting dose reduction of Capecitabine to 75% is recommended.Administration precautionDOCETAXEL TRIHYDRATE (Docetaxel) must be administered intravenously it is extremely important that the intravenous people or catheter be properly positioned before any DOCETAXEL TRIHYDRATE (Docetaxel) is injected. Leakage into surrounding tissue during intravenous administration of DOCETAXEL TRIHYDRATE (Docetaxel) may cause considerable irritation, local tissue necrosis and / or thrembophlebitis. If extravasation occurs, the injection should be discontinued immediately and any remaining portion of the dose should be introduced into another vein.OVERDOSE :There were a few reports of overdose. There is no known antidote for Docetaxel overdose. In case of overdose, the patients should be kept in a specialized unit and vital functions closely monitored. In case of overdose, exacerbation of adverse events may be expected. The primary anticipated complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed.STORAGE :Do not store above 30oC.Store in the original package in order to protect from light.For storeage conditions of the diluted medicinal product, see section Shelf life.Keep out the reach and sight of children.SHELF LIFE :After opening of the vialEach vial is for single use and should be used immediately after opening. If not used immediately, in-use storage times and conditions are the responsibility of the user.Once added to the infusion bagFrom a microbiological point of view, reconstitution / dilution must take place in controlled and aseptic conditions and the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.Once added as recommended into the infusion bag, the Docetaxel infusion solution, if stored below 25oC, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion IV administration).Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, the solution must no longer be used and shall be discarded.EXPIRY :Do not use later than the date of expiry.PACKAGING AND REGISTRATION NO. :Docetaxel Trihydrate 20 mg/1 mL concentrate for solution for infusion :Box contains 1 vial @ 1 mL Reg. No. GKL1943900749A1Docetaxel Trihydrate 80 mg/4 mL concentrate for solution for infusion :Box contains 1 vial @ 4 mL Reg. No. GKL1943900749A1ON MEDICAL PRESCRIPTION ONLY

Manufactured by :PT CKD OTTO PharmaceuticalsBekasi - IndonesiaRegistered by:PT CKD OTTO PharmaceuticalsBekasi - Indonesia

System organInfections and infestations

Blood and lymphatic system disorders

Immune system disorders

Metabolism and nutrition disorders

Nervous system disorders

Cardiac disorders

Vascular disorders

Respiratory, thoracic, and mediastinal disorders

Gastrointestinal disorders

Skin and subcutaneous tissue disorders

Musculoskeletal and connective tissue disorders

General disorders and administration site conditions

Investigations

Adverse reactionInfection; including sepsis and pneumonia; infection associated withneutropenia

Neutropenia; anemia; febrile Neutropenia; trombocytopenia

Hipersensitivity

Anorexia

Peripheral sensory neuropathy; peripheral motor neuropathy; dysgeusia

Arrythmia; cardiac failure

Hypotension; hypertension; hemorrhage

Dyspnea

Stomatitis; diarrhea; nausea; vomiting; constipation; abdominal paingastrointestinal hemorrhage; Esophagitis

Alopecia; skin reactions; nail disorders

Myalgia; athralgia

Fluid retention; asthenia; pain; infusion site reaction; non-cardiac chestpain

Blood bilirubin increased; blood alkaline phosphatase increased; ASTincreased; ALT increased






Cardiac disorders

Vascular disorders




General disorders and administration site condition

Investigations

Adverse reactionInfection

Neutropenia; anemia; trombocytopenia; febrile neutropenia

Hypersensitivity (not severe)

Anorexia

Peripheral sensory neuropathy; peripheral motor neuropathy

Arrythmia (not severe)

Hypotension

Nausea; stomatitis; vomiting; diarrhea; constipation


Myalgia

Asthenia; fluid retention; pain

Blood bilirubin increased






Cardiac disorders

Vascular disorders





Investigations


Neutropenia; anemia; febrile neutropenia; trombocytopenia

Hypersensitivity

Anorexia


Cardiac failure; arrythmia (not severe)

Hypotension

Stomatitis; diarrhea; vomiting; constipation

Alopecia; nail disorders; skin reactions (not severe)

Myalgia

Asthenia; fluid retention; pain; infusion site reaction

Blood bilirubin increased; blood alkaline phosphatase increased

System organBlood and lymphatic system disorders


Psychiatric disorders


Eye disorders

Cardiac disorders

Vascular disorders

Respiratory, thoracic and mediastinal disorders





Investigations

Adverse reactionNeutropenia; febrile neutropenia (such as febrile neutropenia andantibiotic use) or neutropenic sepsis

Anorexia

Insomnia

Paresthesia; headache; dysgeusia; hypoaesthesia

Lacrimation increased; conjunctivitis

Cardiac failure

Lymphoedema

Epistaxis; pharyngolaryngeal pain; nasopharyngitis; dyspnea; cough;rhinorrhea

Nausea; diarrhea; vomiting; constipation; stomatitis; dyspepsia;abdominal pain

Alopecia; erythema; rash; nail disorders

Myalgia; arthralgia; pain in extremity; bone pain; back pain

Asthenia; oedema peripheral; pyrexia; fatigue; mucosal inflammation;pain influenza like illness: chest pain; chills; lethargy

Weight increased






Cardiac disorders

Vascular disorders





Investigations



Hipersensitivity

Anorexia



Hypotension

Stomatitis; diarrhea; nausea; vomiting; constipation

Alopecia; nail disorders; skin reactions

Myalgia

Asthenia; fluid retention; pyrexia; infusion site reaction; pain

Blood bilirubin increased; ALT increased; AST increased; blood alkalinephosphatase increased

System organInfection and infestations





Eye disorders

Cardiac disorders

Vascular disorders





Reproductive system and breast disorders


Investigations

Adverse reactionInfection; neutropenic infection

Anemia; neutropenia; trombocytopenia; febrile neutropenia

Hypersensitivity

Anorexia

Dysgeusia; peripheral sensory neuropathy; peripheral motor neuropathy;syncope; neurotoxicity; somnolence

Lacrimation increased

Arrythmia; congestive heart failure

Hot flush; hypotension; phlebitis; lymphoedema

Cough

Stomatitis; diarrhea; nausea; vomiting; constipation;abdominal pain

Alopecia; skin disorders; nail disorders

Myalgia; arthralgia

Amenorrhea

Asthenia; pyrexia; oedema peripheral

Weight increased or decreased





Eye disorders






Investigations

Adverse reactionOral candidiasis

Neutropenia; anemia; trombocytopenia

Anorexia; decreased appetite; dehydration

Dysgeusia; paraesthesia; dizziness; headache; peripheral neuropathy


Pharyngolaryngeal pain; dyspnea; cough; epistaxis

Stomatitis; diarrhea; nausea; vomiting; constipation; abdominalpain; dyspepsia; abdominal pain upper; dry mouth

Hand - foot syndrome; alopecia; nail disorders; dermatitis;rash erythematous; nail discolouration; onycholysis

Myalgia; arthralgia; pain in extremity; back pain

Asthenia; pyrexia; fatigue / weakness; oedema peripheral;lethargy; pain

Weight decreased; blood bilirubin increased






Eye disorders

Cardiac disorders







Hypersensitivity

Anorexia

Peripheral sensory neuropathy; dysgeusia; peripheral motor neuropathy


Cardiac left ventricular function disease

Dyspnea; cough; epistaxis

Stomatitis / pharyngitis; diarrhea; nausea; vomiting

Alopecia; nail disorders (not severe); exfoliative rash

Arthralgia; myalgia

System organInfection and infestation

Neoplasm benign, malignant and unspecified(including cysts and polyps)





Eye disorders

Ear and labyrinth disorders

Cardiac disorders

Vascular disorders





Investigations

Adverse reactionInfections; neutropic infections

Cancer pain


Hypersensitivity (no severe)

Anorexia

Dysgeusia / parosmia; peripheral sensory neuropathy; dizziness


Hearing impaired

Myocardial ischemia; arrythmia

Vena disorders

Stomatitis; diarrhea; nausea; vomiting; constipation; esophagitis /dysphagia / odynophagia; abdominal pain; dyspepsia; gastrointestinalhaemorrhage

Alopecia; rash pruritic; dry skin; skin exfoliative

Myalgia

Lethargy; pyrexia; fluid retention; oedema

Weight increased






Eye disorders


Cardiac disorders




Adverse reactionNeutropenic infection; infection


Hypersensitivity

Anorexia

Peripheral sensory neuropathy; dizziness; peripheral motor neuropathy


Hearing impaired

Arrythmia

Stomatitis; diarrhea; nausea; vomiting; constipation; gastrointestinalpain; oesophagitis / dysphagia / odynophagia

Alopecia; rash pruritus; nail disorders; skin exfoliation

Lethargy; fever; fluid retention

Toxicity

Diarrhea grade 3

Diarrhea grade 4

Stomatitis / mucositisgrade 3


Dose adjustment

First episode : reduce 5-FU dose by 20%Second episode : then reduce Docetaxel dose by 20%

First episode : reduce Docetaxel and 5-FU doses by 20%Second episode : discontinue treatment

First episode : reduce 5-FU dose by 20%Second episode : stop 5-FU only, at all subsequent cyclesThird episode : reduce Docetaxel dose by 20%

First episode : stop 5-FU only, at all subsequent cyclesSecond episode : reduce Docetaxel dose by 20%

For packaging vendor2 / 2

Keterangan Dasar

Ukuran : 380 x 350 mmBahan : HVS 60 g/m2

Warna : Hitam (cetak 2 muka / bolak-balik)

For registration1 / 2

Baca semua leaflet ini dengan seksama sebelum Anda mulai menggunakan obat ini karena mengandung informasi penting untuk Anda- Simpan leaflet ini. Anda mungkin perlu untuk membacanya lagi.- Jika Anda memiliki pertanyaan lebih lanjut, tanyakan kepada dokter, apoteker rumah sakit atau perawat Anda.- Jika Anda mendapatkan efek samping, bicarakan pada dokter, apoteker rumah sakit atau perawat Anda. Hal ini termasuk efek samping yang mungkin tidak tercantum dalam leaflet ini.

Apa yang ada di leaflet ini :1. Apa DOCETAXEL TRIHYDRATE dan apa kegunaannya2. Apa yang perlu Anda ketahui sebelum Anda menggunakan DOCETAXEL TRIHYDRATE3. Cara menggunakan DOCETAXEL TRIHYDRATE4. Kemungkinan efek samping5. Bagaimana untuk menyimpan DOCETAXEL TRIHYDRATE6. Isi dari kemasan dan informasi lainnya

1. APA DOCETAXEL TRIHYDRATE (DOCETAXEL) DAN APA KEGUNAANNYA Nama obat ini adalah DOCETAXEL TRIHYDRATE. Nama umumnya adalah docetaxel. Docetaxel adalah zat yang berasal dari jarum pohon yew. Docetaxel termasuk dalam kelompok obat anti-kanker yang disebut taksoid.

Kegunaan Docetaxel Trihydrate :- Kanker payudara DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan doxorubicin dan cyclophosphamide diindikasikan untuk pengobatan adjuvant untuk pasien dengan: • kanker payudara node-positif yang dapat dioperasi. • kanker payudara node-negatif yang dapat dioperasi.

Untuk pasien dengan kanker payudara node-negatif yang dapat dioperasi, pengobatan adjuvant harus dibatasi untuk pasien yang memenuhi syarat untuk menerima kemoterapi sesuai dengan kriteria yang telah ditetapkan secara internasional untuk terapi utama kanker payudara dini.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan doxorubicin diindikasikan untuk pengobatan pasien dengan kanker payudara stadium lanjut atau metastasis yang belum pernah menerima terapi sitotoksik untuk kondisi ini.

DOCETAXEL TRIHYDRATE (docetaxel) monoterapi diindikasikan untuk pengobatan pasien dengan kanker payudara stadium lanjut atau metastasis setelah kegagalan terapi sitotoksik. Kemoterapi sebelumnya harus telah menyertakan salah satu anthracycline atau zat alkilasi.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan trastuzumab diindikasikan untuk pengobatan pasien dengan kanker payudara metastasis dengan tumor yang diekspresikan berlebih HER2 dan yang sebelumnya belum menerima kemoterapi untuk penyakit metastasis.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan capecitabine diindikasikan untuk pengobatan pasien dengan stadium lanjut atau kanker payudara metastasis setelah gagal kemoterapi sitotoksik; Terapi sebelumnya harus telah menyertakan salah satu anthracycline.

- Kanker paru-paru non-sel kecil DOCETAXEL TRIHYDRATE (docetaxel) diindikasikan untuk pengobatan pasien kanker paru-paru non-sel kecil dengan stadium lanjut atau metastasis setelah gagal kemoterapi sebelumnya.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan cisplatin diindikasikan untuk pengobatan pasien dengan dioperasi, kanker paru-paru non-sel kecil lanjut secara lokal atau metastasis, pada pasien yang belum pernah menerima kemoterapi untuk kondisi ini.

DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan carboplatin merupakan pilihan pengobatan untuk terapi berbasis cisplatin.

- Kanker prostat DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan prednisone atau prednisolone diindikasikan untuk pengobatan pasien dengan kanker prostat metastasis hormon refraktori.

- Kanker lambung DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan cisplatin dan 5-fluorouracil diindikasikan untuk pengobatan pasien dengan kanker lambung metastasis, termasuk kanker pada gastroesophageal junction, yang belum menerima kemoterapi sebelumnya untuk penyakit metastasis.

- Kanker kepala dan leher DOCETAXEL TRIHYDRATE (docetaxel) dalam kombinasi dengan cisplatin dan 5-fluorouracil diindikasikan untuk induksi pengobatan pasien dengan kanker sel squamous lanjut secara lokal dari kepala dan leher

- Kanker rahim Docetaxel Trihydrate (docetaxel) diindikasikan untuk pengobatan pasien dengan kanker metastasis dari ovarium setelah kegagalan lini pertama atau kemoterapi berikutnya.2. APA YANG ANDA HARUS TAHU SEBELUM MENGGUNAKAN DOCETAXEL TRIHYDRATE Anda tidak boleh diberikan DOCETAXEL TRIHYDRATE jika • Anda alergi (hipersensitif) terhadap docetaxel atau bahan lain dari DOCETAXEL TRIHYDRATE. • Jumlah sel darah putih terlalu rendah. • Anda memiliki penyakit hati yang berat.

Peringatan dan tindakan pencegahanSebelum setiap pengobatan dengan DOCETAXEL TRIHYDRATE, Anda harus menjalani tes darah untuk memeriksa apakah Anda memiliki cukup sel darah dan fungsi hati yang cukup untuk menerima DOCETAXEL TRIHYDRATE. Dalam kasus gangguan sel darah putih, Anda mungkin mengalami demam atau infeksi yang berhubungan.Anda akan diminta untuk mengambil premedikasi yang terdiri dari kortikosteroid yang

diminum seperti dexamethasone, satu hari sebelum pemberian DOCETAXEL TRIHYDRATE dan akan terus berlanjut selama satu atau dua hari setelah itu untuk meminimalkan efek tertentu yang tidak diinginkan yang mungkin terjadi setelah pemberian infus DOCETAXEL TRIHYDRATE dalam reaksi alergi dan retensi cairan tertentu (pembengkakan tangan, kaki atau peningkatan berat badan). Selama perawatan, Anda mungkin akan diberi obat-obatan lain untuk menjaga jumlah sel darah Anda. DOCETAXEL TRIHYDRATE mengandung alkohol. Diskusikan dengan dokter jika Anda menderita ketergantungan alkohol atau gangguan hati. Lihat juga bagian "DOCETAXEL TRIHYDRATE berisi etanol (alkohol)" di bawah ini.

Obat-obatan lain dan DOCETAXEL TRIHYDRATETolong beritahu dokter atau apoteker rumah sakit jika Anda menggunakan atau baru saja mengkonsumsi obat lain, termasuk obat-obatan yang diperoleh tanpa resep. Hal ini karena DOCETAXEL TRIHYDRATE atau obat lain tidak dapat bekerja dengan baik seperti yang diharapkan dan Anda akan lebih mungkin terkena efek samping.

Kehamilan, menyusui dan kesuburanMintalah dokter Anda untuk memberi saran sebelum diberikan obat apapun.DOCETAXEL TRIHYDRATE TIDAK boleh diberikan jika Anda sedang hamil kecuali dengan jelas ditunjukkan oleh dokter Anda.Anda tidak boleh hamil selama pengobatan dengan obat ini dan harus menggunakan metode kontrasepsi yang efektif selama terapi, karena DOCETAXEL TRIHYDRATE mungkin berbahaya bagi bayi yang belum lahir. Jika kehamilan terjadi selama pengobatan Anda, Anda harus segera memberitahu dokter Anda. Anda tidak boleh menyusui saat Anda menerima pengobatan dengan dengan DOCETAXEL TRIHYDRATE.Jika Anda seorang pria yang dirawat dengan DOCETAXEL TRIHYDRATE Anda disarankan untuk tidak punya anak selama dan sampai 6 bulan setelah pengobatan dan mencari rekomendasi untuk konservasi sperma sebelum perawatan karena docetaxel dapat mengu-bah kesuburan pria.

Mengemudi dan menggunakan mesinTidak ada studi tentang efek pada kemampuan mengemudi dan menggunakan mesin yang telah dilakukan.

DOCETAXEL TRIHYDRATE mengandung etanol (alkohol)Produk obat ini mengandung 0.42 ml etanol (alkohol) setiap ml vialnya.Berbahaya bagi mereka yang menderita alkoholisme.Untuk dipertimbangkan jika Anda wanita hamil atau jika Anda sedang menyusui, anak-anak dan kelompok berisiko tinggi seperti pasien dengan penyakit hati, atau epilepsi.Jumlah alkohol dalam produk obat dapat mengubah efek obat lain.Jumlah alkohol dalam obat ini dapat mengganggu kemampuan Anda mengemudi atau menggunakan mesin.

3. BAGAIMANA MENGGUNAKAN DOCETAXEL TRIHYDRATEDOCETAXEL TRIHYDRATE akan diberikan kepada Anda oleh seorang tenaga kesehatan.

Dosis pada umumnyaDosisnya akan tergantung pada berat badan dan kondisi umum Anda. Dokter Anda akan menghitung luas permukaan tubuh Anda dalam meter persegi (m2) dan akan menentukan dosis yang harus Anda terima.

Metode dan rute pemberianDOCETAXEL TRIHYDRATE akan diberikan melalui infus ke dalam salah satu pembuluh darah Anda (rute IV). Infus akan berlangsung sekitar satu jam selama Anda dirawat di rumah sakit.

Frekuensi pemberianAnda biasanya harus menerima infus Anda sekali setiap 3 minggu.

Dokter Anda dapat mengubah dosis dan frekuensi dosis tergantung pada tes darah, kondisi umum dan respons Anda terhadap DOCETAXEL TRIHYDRATE. Secara khusus, silahkan beritahu dokter Anda jika terjadi diare, luka di mulut, berasa baal atau kesemutan, demam dan berikan hasil tes darah kepada dokter Anda. Informasi tersebut akan memungkinkan dokter Anda untuk memutuskan apakah pengurangan dosis diperlukan. Jika Anda memiliki pertanyaan lebih lanjut pada penggunaan obat ini, tanyakan kepada dokter atau apoteker rumah sakit Anda.

4. KEMUNGKINAN EFEK SAMPINGSeperti obat-obatan lainnya, obat ini dapat menyebabkan efek samping, meskipun tidak semua orang merasakannya.

Dokter Anda akan membicarakan hal ini kepada Anda dan akan menjelaskan potensi risiko dan manfaat dari perawatan Anda.Reaksi yang paling sering dilaporkan dari penggunaan DOCETAXEL TRIHYDRATE tunggal adalah: penurunan jumlah sel darah merah atau sel darah putih, kerontokan rambut, mual, muntah, luka pada mulut, diare, dan kelelahan.Tingkat keparahan efek samping dari DOCETAXEL TRIHYDRATE dapat meningkat ketika DOCETAXEL TRIHYDRATE diberikan dalam kombinasi dengan agen kemoterapi lain.

Selama infus di rumah sakit reaksi alergi berikut (dapat terjadi lebih dari 1 dari 10 orang) :• wajah terasa panas, reaksi kulit, gatal• dada sesak, kesulitan bernafas• demam atau kedinginan• sakit punggung• tekanan darah rendah

Reaksi yang lebih parah dapat terjadi.

Staf rumah sakit akan memantau kondisi Anda dengan erat selama pengobatan. Katakan kepada mereka segera jika Anda melihat salah satu dari efek ini.

Antara infus DOCETAXEL TRIHYDRATE, yang berikut ini dapat terjadi, dan frekuensinya mungkin berbeda dengan kombinasi obat-obatan yang diterima:Sangat umum (dapat terjadi lebih dari 1 dari 10 orang) :• infeksi, penurunan jumlah sel darah merah (anemia), atau sel darah putih (yang penting dalam melawan infeksi) dan trombosit• demam: jika terjadi demam, Anda harus memberitahu dokter Anda segera• reaksi alergi seperti dijelaskan di atas• hilangnya nafsu makan (anoreksia)• kesulitan untuk tidur• perasaan baal atau kesemutan atau nyeri pada sendi atau otot• sakit kepala• perubahan pada indera perasa• radang mata atau melimpahnya air mata• pembengkakan yang disebabkan oleh gangguan aliran limfa• sesak napas• gangguan aliran pada hidung; radang pada tenggorokan dan hidung; batuk

• perdarahan dari hidung• luka di mulut• gangguan pada perut seperti mual, muntah dan diare, sembelit• nyeri pada perut• gangguan pencernaan• rambut rontok (dalam banyak kasus pertumbuhan rambut normal akan kembali)• kemerahan dan pembengkakan pada telapak tangan atau telapak kaki Anda yang dapat menyebabkan kulit Anda mengelupas (ini juga dapat terjadi pada lengan, wajah, atau tubuh)• perubahan warna kuku, yang mungkin akan terlepas• Sakit pada otot dan nyeri, sakit punggung atau nyeri tulang• perubahan atau tidak adanya menstruasi• pembengkakan tangan, kaki, betis• kelelahan, atau gejaia seperti flu• bertambah atau berkurangnya berat badan.

Umum (dapat terjadi lebih dari 1 dari 10 orang) :• kandidiasis (infeksi jamur yang disebabkan oleh jamur Candida albicans) pada mulut• dehidrasi• pusing• hilangnya fungsi pendengaran• penurunan tekanan darah, detak jantung yang tidak teratur atau cepat• gagal jantung• radang pada esophagus• mulut kering• kesulitan atau sakit saat menelan• perdarahan• peningkatan enzim hati (maka dibutuhkan untuk tes darah secara rutin)

Tidak umum (dapat terjadi lebih dari 1 dari 100 orang) :• pingsan• pada tempat suntikan: reaksi kulit, flebitis (radang pembuluh darah) atau pembengkakan• radang usus, usus kecil, perforasi usus• pembekuan darah

Frekuensi tidak diketahui :• Penyakit paru interstisial (radang paru-paru menyebabkan batuk dan sulit bernafas, peradangan paru-paru juga bisa berkembang saat terapi doksetasel digunakan dengan radioterapi)• Pneumonia (infeksi paru-paru)• Fibrosis paru (jaringan parut dan penebalan paru-paru dengan sesak napas)• Penglihatan kabur akibat pembengkakan retina di mata (cystoid macular edema)• Penurunan natrium, kalium, magnesium dan / atau kalsium dalam darah anda (gangguan keseimbangan elektrolit)• Ventrikel aritmia atau ventrikel takikardia (manifestasi sebagai detak jantung yang tidak teratur dan / atau cepat, sesak napas hebat, pusing, dan / atau pingsan). Beberapa gejala ini bisa serius. Jika ini terjadi, segera beri tahu dokter anda• Reaksi di tempat suntikan di tempat reaksi sebelumnya.

Jika Anda mengalami efek samping beri tahukan dokter, apoteker rumah sakit atau perawatAnda. Hal ini termasuk efek samping yang mungkin tidak tercantum dalam leaflet ini.

5. BAGAIMANA MENYIMPAN DOCETAXEL TRIHYDRATEJauhkan obat ini dari pandangan dan jangkauan anak-anak.Obat ini tidak boleh digunakan setelah tanggal kadaluwarsa yang tercantum pada kotak dan label vial setelah kadaluwarsa, tanggal kadaluwarsa mengacu pada tanggal terakhir bulan tersebut.Jangan simpan pada suhu di atas 30°C.Simpan dalam kemasan asli untuk melindungi dari cahaya.Gunakan botol segera setelah pembukaannya. Jika tidak langsung digunakan, waktupenyimpanan dalam penggunaan dan kondisi adalah tanggung jawab pengguna.Dari sudut pandang mikrobiologi, rekonstitusi / pengenceran harus berlangsung dalam kondisi yang terkendali dan aseptik.Gunakan obat segera setelah ditambahkan ke dalam kantong infus. Jika tidak langsung digunakan, waktu penyimpanan dalam penggunaan dan kondisi adalah tanggung jawab pengguna dan biasanya tidak lebih lama dari 6 jam pada suhu di bawah 30°C termasuk infus satu jam.Larutan infus Docetaxel bersifat jenuh, karena itu mungkin mengkristal dari waktu ke waktu. Jika muncul kristal, larutan tersebut tidak boleh digunakan dan harus dibuang.Jangan membuang obat-obatan melalui air limbah. Tanyakan apoteker Anda bagaimana untuk membuang obat-obatan Anda tidak lagi digunakan. Langkah-langkah ini akan membantu melindungi lingkungan.

6. ISI KEMASAN DAN INFORMASI LAIN Apa isi DOCETAXEL TRIHYDRATE- Zat aktifnya adalah docetaxel (sebagai trihidrat). Setiap ml larutan konsentrat untuk infus mengandung 20 mg docetaxel.- Bahan-bahan lainnya adalah polisorbat 80, etanol anhidrat dan asam sitrat anhidrat.

Bagaimana rupa DOCETAXEL TRIHYDRATE dan isi kemasanLarutan konsentrat DOCETAXEL TRIHYDRATE untuk infus adalah larutan kuning sampai coklat kuning. • Docetaxel Trihydrate 20 mg/1 mL Konsentrat ini tersedia dalam vial gelas bening tidak berwarna berukuran 6 ml dengan segel karet dan flip-off alumunium berwarna hijau yang terhubung dengan tutup polipropilen. Setiap kotak berisi 1 vial 1 ml konsentrat (20 mg docetaxel).• Docetaxel Trihydrate 80 mg/4 mL Konsentrat ini tersedia dalam vial gelas bening tidak berwarna berukuran 6 ml dengan segel karet dan flip-off alumunium berwarna merah yang terhubung dengan tutup polipropilen. Setiap kotak berisi 1 vial 4 ml konsentrat (80 mg docetaxel).

Produsen :PT CKD OTTO PharmaceuticalsBekasi - Indonesia

Diregistrasikan oleh : PT CKD OTTO PharmaceuticalsBekasi - Indonesia

Peringatan : Cytotoxic Agent


Larutan Konsentrat untuk Infus

kdoe

kem

asan

Nama Bahan Kemas

Kode Bahan Kemas

Menggantikan Kode

ARTWORKLeaflet Docetaxel

-

-

For registration2 / 2


Concentrate for Solution for Infusion

Warning : Cytotoxic Agent

COMPOSITION :Docetaxel Trihydrate 20 mg/1 mLEach mL of concentrate contains 20 mg Docetaxel as Trihydrate. One vial of 1 mL of concentrate contains 20 mg of Docetaxel and Ethanol 0.42 mL.Docetaxel Trihydrate 80 mg/4 mLEach mL of concentrate contains 20 mg Docetaxel as Trihydrate. One vial of 4 mL of concentrate contains 80 mg of Docetaxel and Ethanol 0.42 mL.PHARMACEUTICAL FORM :Concentrate for solution for infusion (sterile concentrate).The concentrate is a pale yellow to brownish-yellow solution.MECHANISM OF ACTION :PharmacologyDocetaxel is an antineoplastic agents which acts by promoting the assembly of tubulin into stable microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The binding of Docetaxel to microtubules does not alter the number of protofilaments.Docetaxel is schedule independent and has a broad spectrum of experimental antitumour activity against advanced murine and human grafted tumours.INDICATION :Breast Cancer• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Doxorubicin and Cyclophosphamide is indicated for the adjuvant treatment of patients with : o operable node-positive breast cancer o operable node-negative breast cancer• For patients with operable node negative breast cancer, adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition.• DOCETAXEL TRIHYDRATE (Docetaxel) monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an Anthracycline or an alkylating agent.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumors over express HER2 and who previously have not received chemotherapy for metastatic disease.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Capecitabine indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an Anthracycline.Non Small Cell Lung Cancer• DOCETAXEL TRIHYDRATE (Docetaxel) is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not previously received chemotherapy for this condition.• DOCETAXEL TRIHYDRATE (Docetaxel) in combination with Carboplatin represents a treatment option to Cisplatin based therapy.Prostate CancerDOCETAXEL TRIHYDRATE (Docetaxel) in combination with Prednison or Prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer.Gastric AdenocarcinomaDOCETAXEL TRIHYDRATE (Docetaxel) in combination with Cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease.Head and neck cancerDOCETAXEL TRIHYDRATE (Docetaxel) in combination with Cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.Ovarian cancerDOCETAXEL TRIHYDRATE (Docetaxel) is indicated for the treatment of patients with metastatic carcinoma of the ovary after failure of first line or subsequent chemotherapy.CONTRAINDICATION :• Hypersensitivity reactions to the active substance or to any of the excipients.• Patients with baseline neutrophil count of < 1,500 cells/mm3.• Patients with severe liver impairment (see “Special warnings and special precautions for use” and “Posology and method of and method of administration sections”).• Contraindications for other medicinal products also apply when combined with Docetaxel.ADVERSE REACTION :The most commonly adverse reaction was neutropenia, which was reversible and not cumulative. The median day to nadir was 7 days and the median duration of severe neutropenia (< 500 cells/mm3) was 7 days, anemia, alopecia, nausea, vomiting, stomatitis, diarrhoea and asthenia. The severity of adverse events of Docetaxel may be increased when Docetaxel is given in combination with other chemotherapeutic agents.The following adverse reactions are frequently observed with Docetaxel :Immune system disorders :Hypersensitivity reactions have generally occurred within a few minutes following the start of the infusion of Docetaxel and were usually mild to moderate. The most frequently reported symptoms were flushing, rash with or without pruritus, chest tightness, back pain, dyspnea and fever or chills. Severe reactions were characterized by hypotension and / or bronchospasm or generalized rash / erythema (see “Special warnings and precautions for use”).Nervous system disorders :The development of severe peripheral neurotoxicity requires a reduction of dose (see “Posology and method of administration” and “Special warnings and precautions for use”). Mild to moderate, neuro-sensory signs are characterized by paresthesia, dysesthesia or pain including burning. Neuro-motor events are mainly characterized by weakness.Skin and subcutaneous tissue disorders :Reversible cutaneous reaction have been observed and were generally considered as mild to moderate. Reactions were characterized by rash including localized eruption mainly on the feet and hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently associated with pruritus. Eruptions generally occurred within one week after the Docetaxel infusion. Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to interruption or discontinuation of Docetaxel treatment were reported (see “Posology and method of administration” and “Special warnings and precautions for use”). Severe nail disorders are characterized by hypo- or hyperpigmentation and sometimes pain and onycholysis.General disorders and administration site conditions :Infusion site reactions were generally mild and consisted of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis or extravasation and swelling of the vein.Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower extremities and may become generalized with a weight gain of 3 kg or more. Fluid retention is cumulative in incidence and severity (see “Special warnings and precautions for use”).Docetaxel 100 mg/m2 as a single agent :

Blood and lymphatic system disorders :Bleeding episodes accompanied by thrombocytopenia.Nervous system disorders :The data show a state of reversible occurred in patients who developed neurotoxicity following Docetaxel treatment at 100 mg/m2 as a single agent. These event spontaneously reversible within 3 months.Skin and subcutaneous tissue disorders :One case of alopecia non reversible at the end of the study. Cutaneous reactions were reversible within 21 days.Docetaxel 75 mg/m2 as a single agent :

Docetaxel 75 mg/m2 combination with Doxorubicin :

Docetaxel 75 mg/m2 combination with Cisplatin :

Docetaxel 100 mg/m2 combination with Trastuzumab :

Blood and lymphatic system disorders :Increased haematological toxicity in patients receiving Trastuzumab and Docetaxel compared with Docetaxel single. It should be noted that the situation was likely not taken into account because Docetaxel single dose of 100 mg/m2 is known to cause neutropenia in patients. The incidence of febrile neutropenia / neutropenic sepsis was also increased in patients treated with Trastuzumab plus Docetaxel.Cardiac disorders :Symptomatic heart failure have been reported in patients receiving Docetaxel plus Trastuzumab compared with patients given a single Docetaxel.Docetaxel 75 mg/m2 combination with Capecitabine :

Docetaxel 75 mg/m2 combination with Prednisone or Prednisolone :

Docetaxel 75 mg/m2 combination with Doxorubicin and Cyclophosphamide :

Docetaxel 75 mg/m2 combination with Cisplatin and 5-fluorouracil for gastric adenocarcinoma cancer :

Docetaxel 75 mg/m2 combination with Cisplatin and 5-fluorouracil for head and neck cancer :

SPECIAL WARNING AND SPECIAL PRECAUTIONS FOR USE :For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as Dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to Docetaxel administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral Dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the Docetaxel infusion (see “Posology and method of administrations”).HaematologyNeutropenia is the most frequent adverse reaction of Docetaxel. Neutrophil nadirs occurred at a median of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of complete blood counts should be conducted on all patients receiving Docetaxel. Patients should be retreated with Docetaxel when neutrophils recover to a level ≥ 1,500 cells/mm3 (see “Posology and method of administrations”).In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of Docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use appropriate symptomatic measures or recommended (see “Posology and method of administrations”).In patients treated with Docetaxel in combination with Cisplatin and 5-fluorouracil (TCF), febrile neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patient receiving TCF should be closely monitored (see “Posology and method of administrations” and “Adverse Reaction”).In patients treated with Docetaxel in combination with Doxorubicin and Cyclophosphamide (TAC), febrile neutropenia

and / or neutropenic infection occurred at lower rates when patients received primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be closely monitored (see “Posology and method of administrations” and “Adverse Reaction”).Gastrointestinal reactionsCaution is recommended for patients with neutropenia, particularly at risk for developing gastrointestinal complications. Enterocolitis could develop at any time, and could lead to death as early as on the first day of onset. Patients should be closely monitored for early manifestations of serious gastrointestinal toxicity (see sections Dosage and administration, Precaution - Haematology, Undesirable effect).Hypersensitivity reactionsPatients should be observed closely for hypersensitivity reactions especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of Docetaxel, thus facilities for the treatment of hypotension and bronchospasm should be available. If hypersensitivity reaction occur, minor symptoms such as flushing or localized cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe hypotension, bronchospasm or generalised rash / erythema require immediate discontinuation of Docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions should not be re-challenged with Docetaxel.Patients who have previously experienced a hypersensitivity reaction to Paclitaxel may be at risk to develop hypersensitivity to Docetaxel, including more severe hypersensitivity reaction. These patients should be closely monitored during initiation of Docetaxel therapy.Cutaneous reactionsLocalized skin erythema of the extremities (palms of the hands and soles of the feet) with oedema followed by desquamation has been observed. Severe symptoms such as eruptions followed by desquamation which lead to interruption or discontinuation of Docetaxel treatment were reported (see “Posology and method of administrations”).Fluid retentionPatients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be monitored closely.Patients with liver impairmentIn patients treated with Docetaxel at 100 mg/m2 as single agent who have serum transaminase levels (ALT and / or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia.Therefore, the recommended dose of Docetaxel in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at baseline and before each cycle (see “Posology and method of administrations”).For patients with serum bilirubin levels > ULN and / or ALT and AST > 3.5 times the ULN concurrent with serum alkaline phosphatase levels > 6 times the ULN. No dose-reduction can be recommended and Docetaxel should not be used unless strictly indicated.In combination with Cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical trial excluded patients with ALT and / or AST > 1.5 x ULN associated with alkaline phosphatase > 2.5 x ULN, and bilirubin > 1 x ULN; for these patients, no dose-reductions can be recommended and Docetaxel should not be used unless strictly indicated.No data are available in patients with hepatic impairment treated by Docetaxel in combination in the other indications.Patients with renal impairmentThere are no data available in patients with severely impaired renal function treated with Docetaxel.Nervous systemThe development of severe peripheral neurotoxicity requires a reduction of dose (see “Posology and method of administrations”).Cardiac toxicityHeart failure has been observed in patients receiving Docetaxel in combination with Trastuzumab, particularly following Anthracycline (Doxorubicin or Epirubicin) - containing chemotherapy. This may be moderate to severe and has been associated with death (see “Adverse Reaction”).When patients are candidates for treatment with Docetaxel in combination with Trastuzumab, they should undergo baseline cardiac assesment. Cardiac function should be further monitored during treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For more details see Summary of Product Characteristics of Trastuzumab.Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in patients treated with Docetaxel in combination regimens including Doxorubicin, 5-fluorouracil and / or Cyclophosphamide (see Section Undesirable Effect). Baseline cardiac assesstment is recommended.Eye disordersCystoid macular oedema (CMO) has been reported in patients treated with Docetaxel, as well as with other taxanes. Patients with impaired vision should undergo a prompt and complete opthalmogic examination. In case CMO is diagnosed, Docetaxel treatment should be discontinued and appropriate treatment initiated (see “Undesirable Effect”).OthersContraceptive measures must be taken by both men and women during treatment and for men at least 6 months after cessation of therapy (see “Pregnancy and Lactation”).The concomitant use of DOCETAXEL TRIHYDRATE with strong CYP3A4 inhibitors (e.g. Ketoconazole, Itraconazole, Clarithromycin, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin and Voriconazole) should be avoided (see “Interaction with other medicinal products and other forms of interaction”).Additional cautions for use in adjuvant treatment of breast cancerComplicated neutropeniaFor patients who experience complicated neutropenia (prolonged neutropenia, febrile neutopenia or infection), G-CSF and dose reduction should be considered (see “Posology and method of administration”).Gastrointestinal reactionsSymptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly.Congestive heart failurePatients should be monitored for symptoms of congestive heart failure during therapy and during the follow up period.LeukaemiaIn the Docetaxel, Doxorubicin and Cyclophosphamide (TAC) treated patients, the risk of delayed myelodysplasia or myeloid leukemia requires haematological follow up.Patients with 4+ nodesThe benefit / risk ratio for TAC in patients with 4+ nodes was not defined fully at the interim analysis.ElderlyThere are no data available in patients > 70 years of age on Docetaxel use in combination with Doxorubicin and Cyclophosphamide.ExcipientsThe amount of ethanol in DOCETAXEL TRIHYDRATE may be harmful in patients suffering from alcoholism and should also be taken into account in pregnant or breast-feeding women, in children and in high-risk groups such as patients with liver disease or epilepsy.Consideration should be given to possible effects on the central nervous system.The amount of ethanol in DOCETAXEL TRIHYDRATE may alter the effects of other medicinal products.The amount of ethanol in DOCETAXEL TRIHYDRATE may impair the ability to drive or use machines (see “Effects on ability to drive and use machines”).Interaction with other medicinal products and other forms of interactionIn vitro studies have shown that the metabolism of Docetaxel may be modified by the concomitant administration of compounds which induce, inhibit or are metabolized by (and thus may inhibit the enzyme competitively) cytochrome P450-3A such as Cyclosporine, Terfenadine, Ketoconazole, Erythromycin and Troleandomycin. As a result, caution should be exercised when treating patients with these medicinal products as concomitant therapy since there is a potential for a significant interaction.In case of combination with CYP3A4 inhibitors, the occurance of DOCETAXEL TRIHYDRATE adverse reactions may increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitors (e.g. Ketoconazole, Itraconazole, Clarithromycin, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin and Voriconazole) cannot be avoided, a close clinical surveillance is warranted and a dose-adjustment of DOCETAXEL TRIHYDRATE (Docetaxel) may be suitable during the treatment with the strong CYP3A4 inhibitor (see Special warnings and precautions for use). In a pharmacokinetic study with 7 patients, the co-administration of Docetaxel with the strong CYP3A4 inhibitor Ketoconazole leads to a significant decrease in Docetaxel clearance by 49%. Docetaxel pharmacokinetics in the presence of Prednisone was studied in patients with metastatic prostate cancer. Docetaxel is metabolized by CYP3A4 and Prednisone is known to induce CYP3A4. No statistically significant effect of Prednisone on the pharmacokinetics of Docetaxel was observed.Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of Docetaxel with concomitantly administered medication has not been investigated formally, in vitro interactions with tightly protein - bound agents such as Erythromycin, Diphenhydramine, Propanolol, Propafenone, Phenytoin, Salicylate, Sulfamethoxazole and Sodium Valproate did not affect protein binding of Docetaxel. In addition, Dexamethasone did not affect protein binding of Docetaxel. Docetaxel did not influence the binding of Digitoxin.The pharmacokinetics of Docetaxel, Doxorubicin and Cyclophosphamide were not influenced by their co-administration. Limited data from a single uncontrolled study were suggestive of an interaction between Docetaxel and Carboplatin. When combined to Docetaxel, the clearance of Carboplatin was about 50% higher than values previously reported for Carboplatin monotherapy.Clinical cases consistent with an increase in Docetaxel toxicity were reported when it was combined with Ritonavir. The mechanism behind this interaction is a CYP3A4 inhibition, the main isoenzyme involved in Docetaxel metabolism by Ritonavir. Based on extrapolation from a pharmacokinetic study with Ketoconazole in 7 patients, consider a 50% Docetaxel dose reduction if patients require co-administration of a strong CYP3A4 inhibitor such as azole antifungals, Ritonavir and some macrolides (Clarithromycin, Telithromycin).PREGNANCY AND LACTATION :There is no information on the use of Docetaxel in pregnant women. Docetaxel has been shown to be both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other cytotoxic medicinal products, Docetaxel may cause foetal harm when administered to pregnant women. Therefore, Docetaxel must not be used during pregnancy unless clearly indicated.Women of childbearing potential / contraceptionWomen of childbearing age receiving Docetaxel should be advised to avoid becoming pregnant and to inform the treating physician immediately should this occur.An effective method of contraception should be used during treatment.In non clinical studies, Docetaxel has genotoxic effects and may alter male fertility. Therefore, men being treated with Docetaxel are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment.LactationDocetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be discontinued for the duration of Docetaxel therapy.Effects on ability to drive and use machinesNo studies on the effects on the ability to drive and use machines have been performed.The amount of ethanol in DOCETAXEL TRIHYDRATE and the side effects of the product may impair the stability to drive or use machines (see section Special warning and Undesirable effect).Therefore, patients should be warned of the potential impact of the side effects of the product on the ability to drive or use machines, and be advised not to drive or use machines if they experiences these side effects during treatment.POSOLOGY AND METHOD OF ADMINISTRATIONS :The use of Docetaxel should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a physician qualified in the use of anticancer chemotherapy (see “Special Precautions for disposal and other handling”).Recommended dose :For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral corticosteroid, such as Dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to Docetaxel administration, unless contraindicated, can be used (see “Special warnings and precautions for use”). Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities.For prostate cancer, given the concurrent use of Prednisone or Prednisolone the recommended premedication regimen is oral Dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the Docetaxel infusion (see “Special warnings and precautions for use”).Docetaxel is administered as one - hour infusion every three weeks.Breast cancerIn the adjuvant treatment of operable node - positive and node - negative breast cancer, the recommended dose of Docetaxel is 75 mg/m2 administered 1-hour after Doxorubicin 50 mg/m2 and Cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustment during treatment).For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of Docetaxel is 100 mg/m2 in monotherapy. In the first line treatment, Docetaxel 75 mg/m2 is given in combination therapy with Doxorubicin (50 mg/m2).In combination with Trastuzumab the recommended dose of Docetaxel is 100 mg/m2 every three weeks, with Trastuzumab administered weekly. In the pivotal trial the initial Docetaxel infusion was started the day following the first dose of Trastuzumab. The subsequent Docetaxel doses were administered immediately after completion of the Trastuzumab infusion, if the preceding dose of Trastuzumab was well tolerated. For Trastuzumab dose and administration, see summary of product characteristics.

In combination with Capecitabine, the recommended dose of Docetaxel is 75 mg/m2 every 3 weeks, combine with Capecitabine at 1,250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks followed by 1-week rest period. For Capecitabine dose calculation according to body surface area, see Capecitabine summary of product characteristics.Non-small cell lung cancerIn chemotherapy naive patients treated for non-small cell lung cancer, the recommended dose regimen is Docetaxel 75 mg/m2 immediately followed by Cisplatin 75 mg/m2 over 30 - 60 minutes. For treatment after failure of prior platinum - based chemotherapy, the recommended dose is 75 mg/m2 as a single agent.Prostate cancerThe recommended dose of Docetaxel is 75 mg/m2. Prednisone or Prednisolone 5 mg orally twice daily is administered continuously.Gastric adenocarcinomaThe recommended dose of Docetaxel is 75 mg/m2 as a 1 hour infusion, followed by Cisplatin 75 mg/m2, as a 1 to 3 hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per day given as a 24-hours continuous infusion for 5 days, starting at the end of the Cisplatin infusion.Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for Cisplatin administration. Prophylactic G-CSF should be used to mitigate the risk of hematological toxicities (see also “Dose adjustment during treatment”).Head and neck cancerPatients must receive premedication with antiemetics and appropriate hydration (prior to and after Cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. All patients on the Docetaxel - containing arm of the studies, received prophylactic antibiotics.• Induction chemotherapy followed by radiotherapy (TAX 323) For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of Docetaxel is 75 mg/m2 as a 1 hour infusion followed by Cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.• Induction chemotherapy followed by chemoradiotherapy (TAX 324) For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of Docetaxel is 75 mg/m2 as 1 hour intravenous infusion on day 1, followed by Cisplatin 100 mg/m2 administered as a 30 minutes to 3 hours infusion, followed by 5-fluorouracil 1,000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.For Cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics.Ovarian cancerThe recommended dose of DOCETAXEL TRIHYDRATE (Docetaxel) is 75 to 100 mg/m2 administered as one - hour infusion every three weeks. A dose of 100 mg/m2 has been show to result in a moderate increase in response rates compared with 75 mg/m2 but is associated with greater toxicity.DOSE ADJUSTMENT DURING TREATMENT :GeneralDocetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm3. In patients who experienced either febrile neutropenia, neutrophil < 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during Docetaxel therapy, the dose of Docetaxel should be reduced from 100 mg/m2 to 75 mg/m2, and / or from 75 mg/m2 to 60 mg/m2. If the patient continues to experience there reactions at 60 mg/m2 the treatment should be discontinued.Adjuvant therapy for breast cancer :Primary G-CSF prophylaxis should be considered in patients who receive Docetaxel, Doxorubicin and Cylophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile neutropenia and / or neutropenic infection should have their docetaxel dose reduced to 60 mg/m2 in all subsequent cycles (see “Special warnings and precautions for use” and “Adverse Reaction”). Patient who experience Grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m2.However in clinical practice neutropenia could occur earlier. Thus the use of G-CSF should be considered function of the neutropenic risk of the patient and current recommendations. Patient who experience grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m2.In combination with cisplatin :For patients who are dosed initially at Docetaxel 75 mg/m2 in combination with Cisplatin and whose nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who experience febrile neutropenia, or in patients with serious non-hematologic toxicities, the Docetaxel dose in subsequent cycles should be reduced to 65 mg/m2. For Cisplatin dose adjustment, see the corresponding summary of product characteristics.In combination with Capecitabine :• For Capecitabine dose modification, see Capecitabine summary of product characteristics.• For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the next Docetaxel / Capecitabine treatment, delay treatment until resolved to Grade 0 - 1 and resume at 100% of the original dose.• For patients developing the second appearance of Grade 2 toxicity, or the first appearance of Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0 - 1 and then resume treatment with Docetaxel 55 mg/m2.• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the Docetaxel dose.• For Trastuzumab dose modifications, see Trastuzumab summary of product characteristics.In combination with Cisplatin and 5-fluorouracil :If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the Docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the Docetaxel dose should be reduced from 60 to 45 mg/m2. In case of Grade 4 thrombocytopenia the Docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should not be retreated with subsequent cycles of Docetaxel until neutrophils recover to a level > 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3. Discontinue treatment if these toxicities persist (see “Special warnings and precautions for use”).Recommended dose modifications for toxicities in patients treated with Docetaxel in combination with Cisplatin and 5-fluorouracil (5-FU).

For Cisplatin and 5-fluorouracil dose adjustment, see the corresponding summary of product characteristics.In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (e.g. day 6 - 15) in all subsequent cycles.SPECIAL POPULATION :Patients with hepatic impairmentBased on pharmacokinetic data with Docetaxel at 100 mg/m2 as single agent, patients who have both elevations of transaminase (ALT and / or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of Docetaxel is 75 mg/m2 (see “Special warnings and precautions for use”). For those patients with serum bilirubin > ULN and / or ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose-reduction can be recommended and Docetaxel should not be used unless strictly indicated.In combination with Cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical trial excluded patients with ALT and / or AST > 1.5 x ULN associated with alkaline phosphatase > 2.5 x ULN, and bilirubin > 1 x ULN; for these patients, no dose - reduction can be recommended and Docetaxel should not be used unless strictly indicated. No data are available in patients with hepatic impairment treated by Docetaxel in combination in the other indications.Pediatric populationDOCETAXEL TRIHYDRATE (Docetaxel) is not recommended for children.ElderlyBased on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. In combination with Capecitabine, for patients 60 years of age or more, a starting dose reduction of Capecitabine to 75% is recommended.Administration precautionDOCETAXEL TRIHYDRATE (Docetaxel) must be administered intravenously it is extremely important that the intravenous people or catheter be properly positioned before any DOCETAXEL TRIHYDRATE (Docetaxel) is injected. Leakage into surrounding tissue during intravenous administration of DOCETAXEL TRIHYDRATE (Docetaxel) may cause considerable irritation, local tissue necrosis and / or thrembophlebitis. If extravasation occurs, the injection should be discontinued immediately and any remaining portion of the dose should be introduced into another vein.OVERDOSE :There were a few reports of overdose. There is no known antidote for Docetaxel overdose. In case of overdose, the patients should be kept in a specialized unit and vital functions closely monitored. In case of overdose, exacerbation of adverse events may be expected. The primary anticipated complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed.STORAGE :Do not store above 30oC.Store in the original package in order to protect from light.For storeage conditions of the diluted medicinal product, see section Shelf life.Keep out the reach and sight of children.SHELF LIFE :After opening of the vialEach vial is for single use and should be used immediately after opening. If not used immediately, in-use storage times and conditions are the responsibility of the user.Once added to the infusion bagFrom a microbiological point of view, reconstitution / dilution must take place in controlled and aseptic conditions and the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.Once added as recommended into the infusion bag, the Docetaxel infusion solution, if stored below 25oC, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion IV administration).Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, the solution must no longer be used and shall be discarded.EXPIRY :Do not use later than the date of expiry.PACKAGING AND REGISTRATION NO. :Docetaxel Trihydrate 20 mg/1 mL concentrate for solution for infusion :Box contains 1 vial @ 1 mL Reg. No.Docetaxel Trihydrate 80 mg/4 mL concentrate for solution for infusion :Box contains 1 vial @ 4 mL Reg. No.ON MEDICAL PRESCRIPTION ONLY

Manufactured by :PT CKD OTTO PharmaceuticalsBekasi - IndonesiaRegistered by:PT CKD OTTO PharmaceuticalsBekasi - Indonesia






Cardiac disorders

Vascular disorders

Respiratory, thoracic, and mediastinal disorders





Investigations

Adverse reactionInfection; including sepsis and pneumonia; infection associated withneutropenia

Neutropenia; anemia; febrile Neutropenia; trombocytopenia

Hipersensitivity

Anorexia



Hypotension; hypertension; hemorrhage

Dyspnea

Stomatitis; diarrhea; nausea; vomiting; constipation; abdominal paingastrointestinal hemorrhage; Esophagitis


Myalgia; athralgia

Fluid retention; asthenia; pain; infusion site reaction; non-cardiac chestpain

Blood bilirubin increased; blood alkaline phosphatase increased; ASTincreased; ALT increased






Cardiac disorders

Vascular disorders





Investigations



Hypersensitivity (not severe)

Anorexia


Arrythmia (not severe)

Hypotension

Nausea; stomatitis; vomiting; diarrhea; constipation


Myalgia

Asthenia; fluid retention; pain

Blood bilirubin increased






Cardiac disorders

Vascular disorders





Investigations


Neutropenia; anemia; febrile neutropenia; trombocytopenia

Hypersensitivity

Anorexia


Cardiac failure; arrythmia (not severe)

Hypotension

Stomatitis; diarrhea; vomiting; constipation

Alopecia; nail disorders; skin reactions (not severe)

Myalgia

Asthenia; fluid retention; pain; infusion site reaction

Blood bilirubin increased; blood alkaline phosphatase increased

System organBlood and lymphatic system disorders


Psychiatric disorders


Eye disorders

Cardiac disorders

Vascular disorders






Investigations

Adverse reactionNeutropenia; febrile neutropenia (such as febrile neutropenia andantibiotic use) or neutropenic sepsis

Anorexia

Insomnia

Paresthesia; headache; dysgeusia; hypoaesthesia


Cardiac failure

Lymphoedema

Epistaxis; pharyngolaryngeal pain; nasopharyngitis; dyspnea; cough;rhinorrhea

Nausea; diarrhea; vomiting; constipation; stomatitis; dyspepsia;abdominal pain

Alopecia; erythema; rash; nail disorders

Myalgia; arthralgia; pain in extremity; bone pain; back pain

Asthenia; oedema peripheral; pyrexia; fatigue; mucosal inflammation;pain influenza like illness: chest pain; chills; lethargy

Weight increased






Cardiac disorders

Vascular disorders





Investigations



Hipersensitivity

Anorexia



Hypotension

Stomatitis; diarrhea; nausea; vomiting; constipation

Alopecia; nail disorders; skin reactions

Myalgia

Asthenia; fluid retention; pyrexia; infusion site reaction; pain

Blood bilirubin increased; ALT increased; AST increased; blood alkalinephosphatase increased






Eye disorders

Cardiac disorders

Vascular disorders





Reproductive system and breast disorders


Investigations

Adverse reactionInfection; neutropenic infection


Hypersensitivity

Anorexia

Dysgeusia; peripheral sensory neuropathy; peripheral motor neuropathy;syncope; neurotoxicity; somnolence


Arrythmia; congestive heart failure

Hot flush; hypotension; phlebitis; lymphoedema

Cough

Stomatitis; diarrhea; nausea; vomiting; constipation;abdominal pain

Alopecia; skin disorders; nail disorders

Myalgia; arthralgia

Amenorrhea

Asthenia; pyrexia; oedema peripheral

Weight increased or decreased





Eye disorders






Investigations

Adverse reactionOral candidiasis

Neutropenia; anemia; trombocytopenia

Anorexia; decreased appetite; dehydration

Dysgeusia; paraesthesia; dizziness; headache; peripheral neuropathy


Pharyngolaryngeal pain; dyspnea; cough; epistaxis

Stomatitis; diarrhea; nausea; vomiting; constipation; abdominalpain; dyspepsia; abdominal pain upper; dry mouth

Hand - foot syndrome; alopecia; nail disorders; dermatitis;rash erythematous; nail discolouration; onycholysis

Myalgia; arthralgia; pain in extremity; back pain

Asthenia; pyrexia; fatigue / weakness; oedema peripheral;lethargy; pain

Weight decreased; blood bilirubin increased






Eye disorders

Cardiac disorders







Hypersensitivity

Anorexia

Peripheral sensory neuropathy; dysgeusia; peripheral motor neuropathy


Cardiac left ventricular function disease

Dyspnea; cough; epistaxis

Stomatitis / pharyngitis; diarrhea; nausea; vomiting

Alopecia; nail disorders (not severe); exfoliative rash

Arthralgia; myalgia


Neoplasm benign, malignant and unspecified(including cysts and polyps)





Eye disorders


Cardiac disorders

Vascular disorders





Investigations

Adverse reactionInfections; neutropic infections

Cancer pain


Hypersensitivity (no severe)

Anorexia

Dysgeusia / parosmia; peripheral sensory neuropathy; dizziness


Hearing impaired

Myocardial ischemia; arrythmia

Vena disorders

Stomatitis; diarrhea; nausea; vomiting; constipation; esophagitis /dysphagia / odynophagia; abdominal pain; dyspepsia; gastrointestinalhaemorrhage

Alopecia; rash pruritic; dry skin; skin exfoliative

Myalgia

Lethargy; pyrexia; fluid retention; oedema

Weight increased






Eye disorders


Cardiac disorders




Adverse reactionNeutropenic infection; infection


Hypersensitivity

Anorexia

Peripheral sensory neuropathy; dizziness; peripheral motor neuropathy


Hearing impaired

Arrythmia

Stomatitis; diarrhea; nausea; vomiting; constipation; gastrointestinalpain; oesophagitis / dysphagia / odynophagia

Alopecia; rash pruritus; nail disorders; skin exfoliation

Lethargy; fever; fluid retention

Toxicity

Diarrhea grade 3

Diarrhea grade 4



Dose adjustment

First episode : reduce 5-FU dose by 20%Second episode : then reduce Docetaxel dose by 20%

First episode : reduce Docetaxel and 5-FU doses by 20%Second episode : discontinue treatment

First episode : reduce 5-FU dose by 20%Second episode : stop 5-FU only, at all subsequent cyclesThird episode : reduce Docetaxel dose by 20%

First episode : stop 5-FU only, at all subsequent cyclesSecond episode : reduce Docetaxel dose by 20%

nama bahan kemas leaflet docetaxel docetaxel ... docetaxel (2...nama obat ini adalah docetaxel...

Documents