Oxaliplatin Hospira 5 mg/ml concentrate for solution for infusion 成份 1 ml oxaliplatin 5 mg - 50 10 ml 50 mg oxaliplatin - 100 20 ml 100 mg oxaliplatin 賦形劑 Tartaric acid NF/Ph.Eur.Sodium Hydroxide NF 劑型 025551 適應症 5-fluorouracil (5-FU) folinic acid (FA) - (Duke s C) - Oxaliplatin Capecitabine / 劑量與用法 劑量限成人使用 Oxaliplatin 85 mg/m 2 2 12 (6 ) Oxaliplatin 85 mg/m 2 2 Oxaliplatin / 3 130 mg/ m 2 ( 65 mg/m 2 ) ( 警語及注意事項 ) oxaliplatin fluoropyrimidines fluoropyrimidine ( 5-fluorouracil) oxaliplatin Oxaliplatin 250~500 ml 5% (50 mg/ml) 0.2 mg/ml 0.70 mg/ml 2~6 oxaliplatin 85 mg/m 2 0.70 mg/ml oxaliplatin 5-fluorouracil 5-FU bolus dose 具有潛在危險性的特殊病人群 - Oxaliplatin ( 禁忌 ) ( 警語及注意事項 ) - phase I study Oxaliplatin oxaliplatin - 65 oxaliplatin 5-FU - oxaliplatin 用法 Oxaliplatin oxaliplatin 250~500 ml 5% 0.2 mg/ml Oxaliplatin 2~6 Oxaliplatin 5-FU 藥品之處理 Oxaliplatin 5% ( 使用指導 ) 禁忌 Oxaliplatin - oxaliplatin - - (myelosuppression) ( <2 10 9 /l <100 10 9 /l) - - (creatinine clearance <30 ml/min)
警語及注意事項 Oxaliplatin oxaliplatin 65 mg/m 2 platinum oxaliplatin oxaliplatin oxaliplatin oxaliplatin oxaliplatin 2 ( 不良反應 ) 6 (RPLS PRES ) ( paresthesia, dysaesthesia)oxaliplatin - 7 oxaliplatin 85 65 mg/m 2 ( ) 75 mg/m 2 ( ) - oxaliplatin 85 65 mg/m 2 ( ) 75 mg/m 2 ( ) - oxaliplatin - oxaliplatin / ( 不良反應 ) / oxaliplatin 5-FU oxaliplatin oxaliplatin ( 上市後的經驗頻率未知 ) ( <1.5 10 9 /l <50 10 9 /l) oxaliplatin/5-fu / / / / 1 1.5 10 9 /l oxaliplatin 5-fluorouracil ( / folinic acid) 5-fluorouracil 5-fluorouracil 4 3 4 ( <1 10 9 /l) 3 4 ( <50 10 9 /l) 5-fluorouracil oxaliplatin 85 65 mg/m 2 ( ) 75 mg/m 2 ( ) oxaliplatin ( 不良反應 ) oxaliplatin oxaliplatin (DIC) DIC oxaliplatin ( 不良反應 ) (dyspnoea crackles) (pulmonary infiltrates) oxaliplatin ( 不良反應 ) (Haemolytic-uraemic syndrome-hus) ( 不良反應 ) oxaliplatin QT Torsade de Points ( 上市後的經驗頻率未知 ) QT QT QT oxaliplatin ( 交互作用 上市後的經驗頻率未知 ) Oxaliplatin oxaliplatin oxaliplatin ( 交互作用 ) Oxaliplatin (DU) oxaliplatin oxaliplatinoxaliplatin ( ) 懷孕及哺乳 oxaliplatin 6 oxaliplatin oxaliplatin ( 不良反應 ) 交互作用 5-FU 85 mg/m 2 oxaliplatin 5-FU oxaliplatin erythromycin, salicylates, granisetron, paclitaxel sodium valproate oxaliplatin QT QT ( 警語及注意事項 ) oxaliplatin ( 警語及注意事項 ) 懷孕及哺乳 oxaliplatin 4 6 Oxaliplatin Oxaliplatin 開車及操作機械能力 oxaliplatin ( ) 不良反應 Oxaliplatin 5-fluorouracil/folinic acid (5 FU/FA) ( ) ( ) ( ) oxaliplatin 5-FU/FA 5-FU/FA ( oxaliplatin 5-FU/FA 416 1108 ) oxaliplatin 55 ( 1/10) ( 1/100 <1/10) ( 1/1,000<1/100) ( 1/10,000<1/1,000) (<1/10,000) ( )
MedDRA Organ system classes * / ( ) ( ) * * / + * / - ( ) ++ +++ Creatinine Alkaline phosphatase ( ) Bilirubin (LDH) lactate dehydrogenase ( ) (DIC) Clostridium difficile * ** + (allergic) ( ) (anaphylactic) ++ ( ) +++ oxaliplatin ( ) 肝膽異常 ( 1/10000) (Hepatic sinusoidal obstruction syndrome) (hepatic veno-occlusive disease) (peliosis hepatis) (nodular regenerative hyperplasia) (perisinusoidal fibrosis) / (transaminases)
腎臟及泌尿道疾患 ( 1/10000) (tubulo-interstitial nephropathy) 血液及淋巴系統異常 (%) Oxaliplatin 85 mg/m 2 5-FU/FA 3 4 3 4 82.2 3 <1 75.6 0.7 0.1 71.4 28 14 78.9 28.8 12.3 71.6 4 <1 77.4 1.5 0.2 5.0 3.6 1.4 0.7 0.7 0.0 1.1 0.7 0.4 1.1 0.6 0.4 55 130 mg/m 2 Oxaliplatin 5-FU ( ) 3 4 (% ) 70.9 7.34 1.8 (% ) 94.5 16.4 5.5 (% ) 72.7 12.7 0 消化道方面異常 (%) Oxaliplatin 85 mg/m 2 5-FU/FA 3 4 3 4 69.9 8 <1 73.7 4.8 0.3 60.8 9 2 56.3 8.3 2.5 49.0 6 1 47.2 5.3 0.5 / 39.9 4 <1 42.1 2.8 0.1 55 / 85 mg/m 2 Oxaliplatin 5-FU ( ) 3 4 (% ) 92.7 10.9 0 (% ) 100 12.7 0 (% ) 81.8 7.3 5.5 / (% ) 54.5 3.6 0 / 3.6% / / oxaliplatin 5-fluorouracil ( 警語及注意事項 ) 免疫系統異常 (%) Oxaliplatin 85 mg/m 2 5-FU/FA 3 4 3 4 / 9.1 1 <1 10.3 2.3 0.6 神經系統異常 Oxaliplatin / 95% ( 警語及注意事項 ) 850 mg/m 2 ( 10 ) 1020/m 2 ( 12 ) 10% 20% 6 87% 3 3% (2.3%) (0.5%) ( 臨床前安全性資料 ) 1% 2% / ( ) ( ) ( 警語及注意事項 ) Lhermitte s oxaliplatin - ( 85.5%) 12.7%
上市後的經驗頻率未知 QT ( 警語及注意事項 ) ( 警語及注意事項 ) ( 4.4 ) 過量 oxaliplatin 藥理學特性 藥效學特性 (platinum) ATC code: L01XA03 (L: anti-neoplastic and immunosuppressants-platinum) Oxaliplatin platinum oxalate 1,2-diaminocyclohexane ( DACH ) platinum Oxaliplatin (a single enantiomer) (SP-4-2)-[1R,2R]-Cyclohexane-1,2-diamine-kN, kn ] [ethanedioato (2-)-kO1,kO2] platinum Oxaliplatin cisplatin oxaliplatin Oxaliplatin 5-FU Oxaliplatin (DNA) DNA (intra and interstrand crosslinks) DNA oxaliplatin (85 mg/m 2 ) 5-fluorouracil/folinic acid (5-FU/FA) 3 - EFC2962 420 5-FU/FA (LV5FU2 210 ) oxaliplatin 5-FU/FA (FOLFOX4 210 ) - 821 irinotecan (CPT-11) 5-FU/ FA EFC4584 5-FU/FA(LV5FU2 275 ) oxaliplatin ( 275 ) oxaliplatin 5-FU/FA (FOLFOX4 271 ) - EFC2964 5-FU/ FA oxaliplain 5-FU/FA (FOLFOX4 57 ) EFC2962 EFC4584 5-FU/FAoxaliplatin 5-FU/FA (PFS)/ (TTP) EFC4584 oxaliplatin 5-FU/FA 5-FU/FA (median overall survivalos) FOLFOX4 LV5FU2 % (95% ) ITT EFC2962 8 EFC4584 ( CPT-11 5-FU/FA ) 6 EFC2964 ( 5-FU/FA ) 12 *NA LV5FU2 22 (16-27) 0.7 (0.0-2.7) P =0.0001 P <0.0001 FOLFOX4 Oxaliplatin 49 (42-46) 11.1 (7.6-15.5) 23 (13-36) 1.1 (0.2-3.2) (PFS)/ (TTP) FOLFOX4 LV5FU2 PFS/TTP (95% ) ITT EFC2962 (PFS) EFC4584 (TTP) ( CPT- 11 5-FU/FA ) EFC2964 ( 5-FU/FA ) *NA LV5FU2 FOLFOX4 Oxaliplatin 6.0 (5.5-6.5) 8.2 (7.2-8.8) Log P =0.0003 2.6 (1.8-2.9) Log P <0.0001 5.3 (4.7-6.1) 5.1 (3.1-5.7) 2.1 (1.6-2.7) FOLFOX4 LV5FU2 (95% ) ITT EFC2962 EFC4584 (TTP) ( CPT-11 5-FU/FA ) EFC2964 ( 5-FU/FA ) *NA LV5FU2 FOLFOX4 Oxaliplatin 14.7 (13.0-18.2) 16.2 (14.7-18.2) Log P =0.12 8.8 9.9 (7.3-9.3) (9.1-10.5) 8.1 Log P =0.09 (7.2-8.7) 10.8 (9.3-12.8)
(EFC4584) oxaliplatin 5-FU/FA 5-FU/FA (27.7% 14.6%p=0.0033) (EFC2962) oxaliplatin MOSAIC (EFC3313) 2246 (899 /Duke s B21347 / Duke s C) 5-FU/FA (LV5FU2 1123 (B2/C=448/ 675) oxaliplatin 5-FU/FA (FOLFOX4 1123 (B2/C=451/672) EFC3313 3 (ITT )* LV5FU2 FOLFOX4 3 (%) (95% ) 73.3 (70.6-75.9) (95% ) 0.76 (0.64-0.89) Stratifield log rank P=0.0008 * 44.2 ( 3 ) 78.7 (76.2-81.1) oxaliplatin 5-FU/FA (FOLFOX4) 3 5-FU/FA (LV5FU2) EFC3313 3 (ITT )* (Duke s B2) (Duke s C) LV5FU2 FOLFOX4 LV5FU2 FOLFOX4 3 (%) (95% ) (95% ) 84.3 (80.9-87.7) 0.79 (0.57-1.09) 87.4 (84.3-90.5) 65.8 (62.2-69.5) 0.75 (0.62-0.9) Log-rank p=0.151 p=0.002 * 44.2 ( 3 ) 72.8 (69.4-76.2) 整體存活率 (ITT 分析 ) MOSAÏC 3 FOLFOX4 85.1% LV5FU2 83.8% 10% FOLFOX4 ( 0.90) (Duke s B2) ( 1.01) FOLFOX4 LV5FU2 92.2% 92.4% (Duke s C) ( 0.87) OLFOX4 LV5FU2 80.4% 78.1% oxaliplatin (85 mg/m 2 2 130 mg/m 2 3 ) HDFL 44.9-56% 5.2-6.2 8.6-12 藥動學特性 130 mg/m 2 oxaliplatin 2 3 1~5 oxaliplatin 85 mg/m 2 2 1-3 platinum platinum oxaliplatin 85 mg/m 2 2 130 mg/m 2 3 Platinum C max μg/ml AUC 0-48 Mg.h/mL AUC μg.h/ml t 1/2ɑ h t 1/2ß h t 1/2ɤ h V ss L CL L/h 85 mg/m 2 0.814 4.19 4.68 0.43 16.8 391 440 17.4 0.193 0.647 1.40 0.35 5.74 406 199 6.35 130 mg/m 2 1.21 8.20 11.9 0.28 16.3 273 582 10.1 0.10 2.40 4.60 0.06 2.90 19.0 261 3.07 AUC 0-48 C max 3 (85 mg/m 2 ) 5 (130 mg/m 2 ) AUCV ss CLCL R0-48 1 C end C max AUCAUC 0-48 V ss CL non-compartmental t 1/2α t 1/2β t 1/2γ compartmental ( 1-3 ) 2 platinum 15% 85% 2 85 mg/m² 3 130 mg/m 2 Oxaliplatin diaminocyclohexane cycle (DACH) cytochrome P450 Oxaliplatin monochloro-dichloro- diaquo-dach platinum Platinum 48 5 54% 3% 腎功能不全的患者 Oxaliplatin Oxaplipatin (CLcr>80 ml/min) (CLcr 50-80 ml/min) (CLcr 30-49 ml/min) (CLcr<30 ml/min) (PUF) platinum 34%57% 79% (PUF) platinum β γ (4)
platinum (PUF) platinum 臨床前安全性資料 ( / ) Oxaliplatin platinum DNA (150 mg/m 2 ) oxaliplatin Oxaliplatin (mutagenic) (clastogenic) oxaliplatin 藥劑學特性 配伍禁忌 oxaliplatin folinic acid 使用與操作指導 Y - 5-fluorouracil trometamol folinic acid trometamol oxaliplatin ( 使用與操作指導 ) - ( ) - ( 使用與操作指導 folinic acid ) - 貯架期 30 2 8 2 貯存時的注意事項 : 貯架期 使用與操作指導 oxaliplatin 使用指導 ( 廢棄物之處理 ) 使用時的注意事項 - - - 5% - - 5-fluorouracil trometamol folinic acid trometamol oxaliplatin 與 folinic acid ( 如 calcium folinate 或 disodium folinate) 併用的操作方法 Oxaliplatin 250 500 ml 5% 85 mg/m 2 5% folinic acid Y 2~6 trometamol folinic acid 與 5-fluorouracil 併用的操作方法 Oxaliplatin fluoropyrimidines 5-fluorouracil oxaliplatin 5-fluorouracil oxaliplatin 注射劑的操作 點滴前之稀釋 oxaliplatin 250 500 ml 5% 0.2 mg/ml 0.7 mg/ml 0.2 mg/ml 2.0 mg/ml 5% glucose 2 8 48 25 24 2 8 24 PVC oxaliplatin 點滴 oxaliplatin prehydration Oxaliplatin 250~500 ml 5% 0.2 mg/ml 2~6 oxaliplatin 5-FU 5-FU oxaliplatin 廢棄物之處理 包裝 50 mg 100 mg 10 ml (Type 1 ) 50 mg oxaliplatin 20 ml (Type 1 ) 100 mg oxaliplatin MoH 20160715-1 製造廠名 :Zydus Hospira Oncology Private Limited 製造廠址 : Pharmez Special Economic Zone, Plot No. 3, Sarkhej-Bavla Road, N.H. No. 8A, Village: Matoda, Taluka: Sanand, District-Ahmedabad-382 213 (Gujarat), India 藥商名稱 : 藥商地址 : 177