ERAXIS - pfizer.com.tw

1 (1A2 2B6 2C9 2C19 2D6 3A) 10 (8) 10 (8) . (14C) anidulafungin anidulafungin 34 (26) 48 (38) ERAXIS ( ) 8 (6) 5 (4) ERAXIS (anidulafungin) . 30% 9 12 (9) 21 (17) ERAXIS ( 34 (26) 36 (29) ERAXIS (anidulafungin) . 10% 1% Cyclosporine (CYP3A4 ) 12 11 (8) 16 (13) ) 12 (9) 20 (16) Anidulafungin . 100 Anidulafungin 6 . 8 . anidulafungin 200 100. / ( 1-8 ) cyclosporine 245 ( ERAXIS 127 fluconazole 118 ) MITT . 219 ( ERAXIS 116 fluconazole ERAXIS ( . ) .. 8 (6). 7 (5). 1 (1). 6 (5). Child-Pugh A B C . anidulafungin . ERAXIS 100 100 .. ERAXIS for Injection 100mg .. / ( 5-8 ) anidulafungin Cmax . cyclosporine anidulafungin AUC . 103 ) . (78%) . ( ) . ERAXIS / ( .. 30 (23). 7 (5). 32 (26). 10 (8). anidulafungin . Child-Pugh C AUC .. ERAXIS 2-8 C (36-46 F) . (anidulafungin) . ( 107 118 . 22% anidulafungin cyclosporine ( ).))

2 (69%) (42%) (25%) . (22%) . ) .. 27 (21). 11 (8). 31 (25). 10 (8). ( . ) .. 25 C (77 F) 96 . 024758 ) anidulafungin Voriconazole (CYP2C19 CYP2C9 CYP3A4 ) (62%) C. glabrata (20%) C. parapsilosis (12%) ERAXIS 27 (21) 25 (20) 2 C-8 C (36 F-46 F) . ( 17 anidulafungin 200 C. tropicalis (11%) (97%) ( ) 7 (5) 13 (10) . ) 100 / voriconazole (ANC > 500) 81% APACHE II 20 ( ) * (SOC) Anidulafungin (<1%) ERAXIS 25 C (77 F) . ERAXIS anidulafungin Anidulafungin 200 ( 400 ) 5 ( ) 24 . ERAXIS (anidulafungin) 50 / 100 / ( anidulafungin voriconazole Cmax AUC 5. anidulafungin 25 C (77 F). (Aspergillus nidulans) ) anidulafungin ( (MITT ) ** ERAXIS Anidulafungin 24 . (lipopeptide) Anidulafungin echinocandin 2 ) ERAXIS Fluconazole a, % ( . 1,3- -D-glucan 2. Anidulafungin Tacrolimus (CYP3A4 ) 35 (N=127) (N=118) (95% ) ) 25 C 24.

3 ERAXIS (anidulafungin) 1-[(4R,5R)-4,5-dihydroxy-N2-[[4"- Anidulafungin (%CV) tacrolimus 5 ( 1 ) anidulafungin n (%) n (%) ERAXIS 929 257 <2% . (pentyloxy)[1,1':4',1"-terphenyl]-4-yl]c arbonyl]-L-ornithine] 200 100 / ( 4-12 96 71 672 ERAXIS 400 . echinocandin B Anidulafungin a Anidulafungin ) ( 13 ) anidulafungin tacrolimus ( ) ( ) ( , ) 633 ( ) ERAXIS 25 C (77 F) . anidulafungin (LD/MD, mg)c Cmax AUC b 94 67 ERAXIS 50 100 481 ERAXIS 10 260 48 72 . ERAXIS (100 ) 100/50 200/100 ( ) ( ) ( ) ( , )c 14 130 ERAXIS 10 25 C (77 F) . (500 ) 80 (polysorbate 80 250 ) Cmax, ss [ / ] ( ) ( ) Rifampin (CYP450 ) Anidulafungin 27 2 82 58 / 3 ( 3 ULN)( 48 72 . ( ) pH / Cmin, ss [ / ] ( ) ( ) anidulafungin rifampin ( ) ( ) ( , )c ) . Anidulafungin C58H73N7O17 AUCss [ / ] ( ) ( ) rifampin anidulafungin 6 71 52 ERAXIS (100 ) fluconazole Anidulafungin 25 C 48.

4 CL [ / ] ( ) rifampin Anidulafungin ( ) ( ) ( , )c CPK QT Anidulafungin 50 / . t1/2, [ ]b ( ) ( ) a ERAXIS fluconazole ERAXIS fluconazole - . a (two compartment H H OH. O Amphotericin B Liposome Anidulafungin 27 b 33 ( ERAXIS 26% fluconazole 29%) 127 118 (100 / ) 5 USPI 201207-2. HO OC5H11 model) AUCss Cmax,ss Cmin,ss ( amphotericin B fluconazole ERAXIS fluconazole . O NH. HO. H NH. ) 1 / amphotericin B anidulafungin c ERAXIS 16-89 Pharmacia & Upjohn Company H O . H3C. N. HN CH3 50 100 / amphotericin B Anidulafungin 6 51% 49% 72% anidulafungin 7000 Portage Road, Kalamazoo, MI 49001, USA. b H. HO. O. O H. H. OH. t 1/2, ( ) MITT 18% / 9% Anidulafungin . H. H3C H. NH. H. N. OH. 6. IV ERAXIS ( 200 177 . c LD/MD / . HO. O. N. H. ERAXIS Fluconazole 100 ) IV fluconazole ( 800 anidulafungin Anidulafungin.)

5 H H. OH. O Anidulafungin echinocandin a 400 ) . H. OH. H Anidulafungin Anidulafungin (glucan synthase) (95% CI) 14 42 Anidulafungin 20 / / ( . ( MITT 127 118 ERAXIS ( 100 / 2 ) . ERAXIS 5% 22%) 1,3- -D-glucan (MITT) fluconazole ERAXIS ) . ( ) 88/116 63/103 . Anidulafungin ( ) ( ) ( , ) Cyclosporine 5-6 . ( ) (65 = / ) (Candida albicans) 1/2 2/4 - 7 5% ERAXIS fluconazole anidulafungin cyclosporine ( . ( 65 = / ) C. glabrata C. parapsilosis C. tropicalis anidulafungin 87/114 61/99 - ) . ( ) ( ) 7 ERAXIS Fluconazole / cyclosporine anidulafungin . Anidulafungin ( ) 5% *,** ( ) . Anidulafungin anidulafungin / 4/6 5/6 - ERAXIS Fluconazole Voriconazole . (MICs) / ( ) 2/2 0/2 - 100 400 anidulafungin voriconazole ( ). anidulafungin HIV (MIC) / - 1/1 - N=131 N=125 200 100 . (IV) Anidulafungin / - 1/1 - N (%) N (%) voriconazole anidulafungin.

6 ( <25%) (HIV) - 0/3 - 130 (99) 122 (98) ( ) 14 . 1 (loading dose Echinocandin - 1/2 - 82 (63) 80 (64) Tacrolimus . ) Anidulafungin (FKS1 FKS2) (point mutations) 1/1 - - 23 (18) 23 (18) anidulafungin ( ) . 2 Anidulafungin Child-Pugh A Candida anidulafungin / 0/1 - - 19 (15) 22 (18) tacrolimus ERAXIS . 1. Anidulafungin B C Anidulafungin / 1/1 - - 9 (7) 11 (9) tacrolimus anidulafungin ERAXIS 5% . (%CV) C 8 (6) 19 (15) ( ) ( ) ERAXIS . a Anidulafungin AUC 8/11 8/15 - 81 (62) 72 (58) Rifampin 5% ( ) . (LD/MD ) b ( ) ( ) ( ) 32 (24) 15 (12) anidulafungin rifampin . 70/35c d 200/100 260/130d e ERAXIS / 24 (18) 23 (18) anidulafungin . (N = 6) (N = 10) (N = 10) 29/127 37/118 - 23 (18) 12 (10) rifampin anidulafungin ( 100 30 . Cmax, ss [ / ] ( ) ( ) ( ) Anidulafungin ERAXIS ( 200 ( %) ( ) 11 (8) 14 (11) ) /.)

7 AUCss ( ) ( ) ( ) ( ) 100 ) fluconazole ( 800 10/127 17/118 - 8 (6) 16 (13) Amphotericin B Liposome 25 C (77 F) 24 . [ / ] anidulafungin Anidulafungin 400 ) APACHE II ( ) ( ) 70 (53) 76 (61) anidulafungin liposomal amphotericin B . CL [ / ] ( ) ( ) ( ) ( 20 > 20) 2/127 5/118 - 23 (18) 23 (18) anidulafungin 5%. t1/2 [ ] ( ) ( ) ( ) C. krusei ( ) ( ) 14 (11) 16 (13) liposomal amphotericin B ( ) ( ). a a ERAXIS fluconazole 7 (5) 6 (5). (2-11 ) 14 42 anidulafungin ( ) . b LD/MD / (12-17 ) anidulafungin 10 67 (51) 55 (44) Table 8. ERAXIS . c 7 ( ) 24 15 (12) 4 (3) . d Cmax AUCss fluconazole 13 (10) 11 (9) B a b . e / / [ ] 9 (7) 7 (6) 20 / / ( . Cmax, ss = 50 100 / ( 3 ( [MITT] ) ERAXIS 8 (6) 2 (2) 100 / 2 4 ) - 100 1 30 100 130 / 90 . AUCss = ) (a successful 66 (50) 46 (37) anidulafungin 100.

8 CL = 3. Anidulafungin global response) ( 15 (12) 14 (11) . t1/2 = Anidulafungin (%CV) ) ( ) 11 (8) 3 (2) 84 /. Anidulafungin 1 / 40-50 a Anidulafungin 7 (5) 14 (11) . (LD/MD / )b 7 (5) 1 (1) ERAXIS 200 2 60 200 260 / 180 . 256 61 (47) 61 (49) 100 . anidulafungin c 2-11 12-17 2-11 12-17 ERAXIS 16-89 33 (25) 24 (19) Anidulafungin anidulafungin . ( ) 30-50 (N = 6) (N = 6) (N = 6) (N = 6) 50% 50% 71% 20% / ERAXIS anidulafungin ERAXIS 15 (12) 14 (11) 84 /. Anidulafungin (>99%) Cmax, ss [ / ] 7% 2% echinocandins 9 (7) 10 (8) ERAXIS . ( ) ( ) ( ) ( ) anidulafungin 14 fluconazole 11 8 (6) 14 (11) a 5% ( ) .. anidulafungin Anidulafungin AUCss fluconazole anidulafungin 8 (6) 8 (6) ERAXIS 16 ( . b / . P450 (CYP450) [ / ] ( ) ( ) ( ) ( ) 7 fluconazole 5 ERAXIS 8 (6) 2 (2) ) / ( . a 5.

9 Anidulafungin CYP450 4 ERAXIS 50 (38) 41 (33) / ) . b LD/MD / 4. 19 (15) 18 (14) ( ) 25 C (77 F) 48 . c 16 . Anidulafungin pH ERAXIS Fluconazole ERAXIS 15 (12) 5 (4) anidulafungin (N=197) 72 . Anidulafungin n (%) n (%) ERAXIS 13 (10) 9 (7) 35% 65 ( ) 18% 75 ( ) . 24 anidulafungin P450 131 125 ERAXIS 48 (37) 45 (36) . (peptidic degradants) CYP 94 (72) 80 (64) / 20 (15) 12 (10).