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PACLITAXEL
Paclitaxel tidak larut dalam air, oleh karena
itu,
paclitaxel
diformulasikan
dalam
polyoxyethylated castor oil (cremophor) 50%
dan ethanol 50%.1,8 Komponen cremophor ini
dapat melarutkan DEHP (bahan plastik PVC),
maka dalam pemberian paclitaxel, set infus
yang digunakan adalah yang non-PVC.5,8 Obat
ini diberikan setiap 3 minggu dengan dosis
175 mg/m2 atau setiap minggu dengan dosis
80 mg/m2.5,9
Farmakokinetik
Pada penelitian awal, paclitaxel yang diberikan
secara infus menunjukkan farmakokinetik
yang bersifat linear, namun penelitianpenelitian berikutnya menunjukkan bahwa
farmakokinetik paclitaxel bersifat non-linear
disebabkan kejenuhan distribusi, metabolisme,
dan eliminasinya.3 Farmakokinetik bersifat
non-linear ini terutama terlihat pada infus
selama 3 jam.3 Karena sifatnya yang non-linear,
tidak terdapat kaitan proporsional antara dosis
dan AUC1. Paclitaxel berikatan dengan protein
plasma (95%)1.
Paclitaxel
Docetaxel
INFO PRODUK
atau carboplatin dalam kombinasi dengan
paclitaxel.15
Paclitaxel
Docetaxel
Farmakokinetik
Nonlinear
Linear
Hati
Hati
Metabolisme
Mekanisme kerja
Dosis
Infus
3 jam
1 jam
1 jam
30 menit
Dexamethasone 20 mg IV
Diphenhydramine 50 mg IV
Cimetidine 300 mg atau Ranitidine 50 mg IV
30-60 menit sebelum kemoterapi
Neutropenia
Neuropati perifer
Bradikardi
Neutropenia
Retensi cairan
Dermatologi
Premedikasi
Toksisitas yang
dominan
791
INFO PRODUK
lebih sering dijumpai pada pasien diabetes,
dengan riwayat neuropati atau yang
sebelumnya telah mendapat kemoterapi.8
Reaksi hipersensitivitas awalnya merupakan
masalah penting dalam pemberian paclitaxel.8
Hal ini disebabkan kandungan cremophor
sebagai pelarutnya.8 Peningkatan durasi
infus dan pemberian premedikasi kemudian
menurunkan insidens reaksi hipersensitivitas
berat sampai kurang dari 5%.8 Kemudian
pada perkembangannya, dilaporkan bahwa
insidens reaksi hipersensitivitas berat sedikit
lebih rendah jika paclitaxel diinfuskan selama
24 jam dibandingkan 3 jam (1% vs 1,6%) pada
pasien yang mendapat premedikasi.8 Terdapat
2 macam cara premedikasi yaitu:5,25
Dexamethasone oral 20 mg 12 dan
6 jam sebelum pemberian paclitaxel,
diphenhydramine 50 mg IV dan cimetidine
300 mg atau ranitidine 50 mg IV 30-60 menit
sebelum pemberian paclitaxel.
Dexamethasone
10
mg/20
mg,
diphenydramine 50 mg, dan cimetidine 300 mg
atau ranitidine 50 mg IV 30-60 menit sebelum
pemberian paclitaxel.
Toksisitas pada jantung pernah dilaporkan pada
pemberian paclitaxel.6,8 Kejadiannya bersifat
asimtomatik dan membutuhkan pemantauan
kardiak secara kontinu.6 Kejadian yang pernah
dilaporkan antara lain aritmia ventrikuler,
bradikardi, hambatan konduksi atrioventrikuler,
bundle branch block, dan iskemik jantung.8
Oleh karena itu, perlu dilakukan pemantauan
tanda-tanda vital (terutama pada jam pertama)
selama infus paclitaxel.8
Kemoterapi Paclitaxel yang Masih dan
Sedang Diteliti
Untuk menghindari penggunaan cremophor,
saat ini dikembangkan fomulasi paclitaxel
non-cremophor yaitu nano albumin particle
bound paclitaxel2 yang sudah disetujui oleh
US FDA untuk kanker payudara dan NSCLC26
dan saat ini masih terus diteliti untuk berbagai
indikasi, serta paclitaxel polymeric micelle yang
sudah disetujui Korean FDA untuk kanker
payudara dan NSCLC,27 yang sampai sekarang
juga masih diteliti untuk berbagai indikasi.
DOCETAXEL
Sama seperti paclitaxel yang tidak larut air,
docetaxel diformulasikan dalam polysorbate
80 (Tween 80).1,7 Komponen ini dilaporkan
berpotensi menimbulkan retensi cairan.7
792
INFO PRODUK
Tabel 2 Perbandingan efek samping paclitaxel dan docetaxel3
Efek Samping
Neutropenia
3 jam
Paclitaxel
24 jam
Docetaxel
1 jam
++
++
Reaksi hipersensitivitas
Rambut rontok
++
++
++
Mukositis
Aritmia jantung
Artralgia/mialgia
Neurosensori
+/-
Edema kumulatif
Kulit/kuku
Ket: (-)= tidak ada, (+/-)= ringan, (+)= sedang, (++)= berat
793
INFO PRODUK
DAFTAR PUSTAKA
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