2016 02 ( 4 ) Lixiaa F.C Tablets 026601 026600 026599 1. 15 30 60 2. 15 30 60edoxaba 6.1 3. 4. 4.1 5 10 Lixiaa VTE) 4.4 ) 4.2 Lixiaa Lixiaa Lixiaa warfari (CrCL) (CrCL) Lixiaa DVT PE 5Lixiaa ( 5.1 ) Lixiaa DVT PE( 4.4 ) VTE) ([CrCL]/) P (P-gp)cyclosporie droedaroe erythromyci ketocoazole 1 NVAF VTE (DVT PE) P (P-gp) ) Cyclosporie droedaroe erythromyci ketocoazole Lixiaa Lixiaa Lixiaa
2 K VKA) Lixiaa Lixiaa Lixiaa K Lixiaa dabigatra rivaroxaba apixaba Lixiaa 5.1 ) Lixiaa (fodapariux) Lixiaa Lixiaa Lixiaa VKA 60Lixiaa K 30 (: ([CrCL] /) P (P-gp) )Lixiaa 15K Lixiaa K 3VKA VKA VKA VKA Lixiaa (85%) Lixiaa 14 Lixiaa VKA3 14Lixiaa 3 Lixiaa Lixiaa VKALixiaa 46% Lixiaa Lixiaa Lixiaa Lixiaa K K Lixiaa Lixiaa Lixiaa Lixiaa Lixiaa (CrCL) /(30) /(60 4.4 ) ( ) Lixiaa Cockcroft-Gault (CrCL/) μmol/l [0.85) [μmol/l] / (140-[0.85) [/] Lixiaa CrCL /)Lixiaa (CrCL/)Lixiaa ( 5.2 ) /) Lixiaa 4.4 5.2 ) Lixiaa ( 4.3 ) Lixiaa ( 4.4 5.2 )
Lixiaa ( 5.2 ) Lixiaa ( 4.4 ) Lixiaa ( 4.4 5.2 ) Lixiaa Lixiaa ( 5.2 ) ( 5.2 ) ( 5.2 ) Lixiaa P (P-gp) Lixiaa P (P-gp)cyclosporie droedaroe erythromyci ketocoazole Lixiaa ( 4.5 ) amiodaroe quiidie verapamil ( 4.5 ) Lixiaa P (P-gp) (HIV) 18 Lixiaa Lixiaa ( 5.2 ) 4.3 6.1 (aeurysms) (eoxapari daltepari ) (fodapariux ) (warfari rivaroxaba apixaba ) 4.5 ) ( 4.6 ) 4.4 Lixiaa Lixiaa ( 1) VKA 2 4.2 ) Lixiaa Lixiaa ( 4.8 Lixiaa 4.8 4.9 ) Lixiaa () VKA / ( 4.8 ) Lixiaa Lixiaa ( 4.9 ) Lixiaa 5.2 ) Lixiaa 4.5 ) /) (CrCL/) / ) 32% 74% 4.2 ) Lixiaa 4.2 5.2 ) NVAF warfarilixiaa ( 5.1 ) 4.2 ) Lixiaa ( 4.2 5.2 ) Lixiaa 4.2 ) Lixiaa ( 4.2 5.2 ) Lixiaa Lixiaa 1 Lixiaa 24 Lixiaa 24 Lixiaa Lixiaa ( 4.2 )
P2Y12 4.5 ) Lixiaa 3 Lixiaa Lixiaa Lixiaa Lixiaa /VTE Lixiaa Xa ( 5.2 ) Lixiaa Xa (PT) (aptt) Lixiaa 4.5 Lixiaa (GI) Lixiaa P (P-gp) Lixiaa P (P-gp)Lixiaa cyclosporie droedaroe erythromyci ketocoazole quiidie verapamil P (P-gp) Lixiaa Lixiaa cyclosporie droedaroe erythromyci ketocoazole 30( 4.2 ) Lixiaa quiidie verapamil amiodaroe ( 4.2 ) Lixiaa P (P-gp) (HIV) P (P-gp) Lixiaa CyclosporieLixiaa Lixiaa C max73% 74% Droedaroe7 5 Lixiaa Lixiaa C max85% 46% Erythromyci 8 7 Lixiaa Lixiaa C max85% 68% Ketocoazole 7 4 Lixiaa Lixiaa C max87% 89% P (P-gp)Lixiaa Quiidie14 ) ( 23 ) 3 Lixiaa Lixiaa 24C max77% 85% Verapamil11 10 Lixiaa Lixiaa C max53% AmiodaroeLixiaa 40% C max66% amiodaroe P (P-gp) Lixiaa P (P-gp) rifampici Lixiaa Lixiaa P (P-gp) ( pheytoi carbamazepie pheobarbital Lixiaa Lixiaa P (P-gp) P (P-gp) Digoxi 114 Lixiaa ( 89 ) 0.25( 1014 )Lixiaa C max17% Lixiaa digoxi C max 28%7% Lixiaa digoxi Lixiaa ( 4.3 ) (ASA)(100 325) Lixiaa (325)Lixiaa C max 35% 32%Lixiaa (325) Lixiaa 100 100/ )thieopyridie Lixiaa warfari 2 ( 4.4 ))Lixiaa thieopyridie( clopidogrel)lixiaa warfari( 4.4 ) Lixiaa Lixiaa Lixiaa C max Lixiaa Lixiaa digoxi Lixiaa C max28%lixiaa quiidie C max verapamil Lixiaa C max14% 16% 4.6 Lixiaa Lixiaa ( 5.3 ) Lixiaa Lixiaa ( 4.3 ) Lixiaa
Lixiaa Lixiaa Lixiaa ( 4.3 )/ Lixiaa ( 5.3 ) 4.7 Lixiaa 4.8 Lixiaa 21,105 ) 8,292 )(Hokusai-VTE) 7,012 Lixiaa ( 30 ) 2.5 Hokusai-VTE 4,118 251 Lixiaa ( 30 )2,256 (32.2%)Hokusai-VTE 1,249 Lixiaa (5.9%)(4.7%)(9.0%)Hokusai-VTE ( 4.4 ) Lixiaa 3(Hokusai-VTE) ) ( ) 3 / / (ALT) () / 1 1 5050
Lixiaa () / ( 4.9 ) Lixiaa ( )VKA / / ( 4.4 ) / Lixiaa / 4.9 Lixiaa Lixiaa Lixiaa Lixiaa Lixiaa Lixiaa Lixiaa Lixiaa 10 14( 5.2 ) ) ( ) 4 30Lixiaa VIIa Lixiaa KLixiaa Lixiaa Lixiaa (desmopressi aprotii) Lixiaa 5. 5.1 ATC Lixiaa XaXa Lixiaa Xa (prothrombiase) Xa (thrombi) Lixiaa 1-2 Lixiaa (C max)xa XaLixiaa PT) Lixiaa rivaroxaba dabigatra apixaba Lixiaa 4 Lixiaa ( Xa aptt) 4 Lixiaa rivaroxaba apixaba3 dabigatradabigatralixiaa Lixiaa dabigatra Lixiaa Lixiaa ( 4.2 ) Lixiaa Lixiaa warfari ( )21,105 CHADS 2 2.8 Lixiaa Lixiaa warfarilixiaa (CrCL/))P (verapamil quiidie droedaroe) (SEE) (CV) (CV) Lixiaa 30 2.5Lixiaa 30 2.860 3015,471 /15,840 / 60 30 19,191 /19,216 / warfari3.0 )68.4%
Lixiaa warfari (mitt) 3 SEE SEELixiaa warfari 1.38)( 4) 4 ENGAGE AF TIMI 48 (mitt) /SEE a (%/yr) b P c (%/yr) b (%/yr) b SEE a warfari a b (%/yr)/ c p1.38 Lixiaa 60 (30 ) 182 1.18 135 0.87 40 0.26 Warfari 232 1.50 144 0.93 76 0.49 ITT( )Lixiaa 296 1.57%) warfari 337(1.80%)warfari Lixiaa HR0.71 1.07 ( P) 30 602.29% warfari ( ) P 3 warfari (Lixiaa warfari) warfari 4) Lixiaa warfari (/SEE) (p 0.0042 mitt ) 5 /SEE CrCL 5 ENGAGE AF-TIMI 48 mitt/see CrCL (/) 1,302 2,093 1,661 927 497 462 Lixiaa 60 63 85 45 27 14 10 1.89 1.51 0.99 1.08 1.01 0.78 mitt *HR 1,305 2,106 1,703 960 469 418 Warfari 67 95 50 26 10 3 2.05 1.70 1.08 0.98 0.78 0.25 HR (95% CI) --* ITT Lixiaa SEEwarfari ( 1.57% 1.80%) HR 0.71 1.07 Lixiaa warfarisee CV (0.76 0.99) 1.00)SEE1.01) Lixiaa (30 )( ) 769 (3.99%)warfari836 ( 1.01)] (Lixiaa warfari)( ) / 0.97)] /1.02)] / 1.40)] Lixiaa (30 )warfari0.97)] (Lixiaa warfari) / CI)0.99)] /0.90)] / 1.46)] ENGAGE AF-TIMI 48 Lixiaa warfari ( 2.75% 0.39%
6 Lixiaa 60warfari (0.21% 0.84) p 6 ENGAGE AF-TIMI 48 - Lixiaa 60 Warfari (30 ) 418 524 (%/yr) a 2.75 3.43 p 0.0009 b 61 132 (%/yr) a 0.39 0.85 32 59 (%/yr) a 0.21 0.38 (%/yr) a 8.67 10.15 c (%/yr) a 14.15 16.40 warfari a (%/yr) b / c 7 8 9 CrCL 7 ENGAGE AF-TIMI 48 a CrCL (/) 1,302 2,093 1,661 927 497 462 Lixiaa 60 96 148 108 29 20 13 3.91 3.31 2.88 1.33 1.70 1.18 1,305 2,106 1,703 960 469 418 Warfari 128 171 119 56 24 21 5.23 3.77 3.08 2.48 2.14 2.08 HR (95% CI) 8 ENGAGE AF-TIMI 48 a CrCL (/) 1,302 2,093 1,661 927 497 462 Lixiaa 60 9 8 10 2 1 2 0.36 0.18 0.26 0.09 0.08 0.18 1,305 2,106 1,703 960 469 418 Warfari 18 23 9 3 5 0 0.72 0.50 0.23 0.13 0.44 0.00 HR (95% CI) --* --* --* 9 ENGAGE AF-TIMI 48 a CrCL (/) 1,302 2,093 1,661 927 497 462 Lixiaa 60 16 19 17 5 2 1 0.64 0.42 0.44 0.23 0.17 0.09 1,305 2,106 1,703 960 469 418 mitt *HR a 3 Warfari 35 51 35 6 3 1 1.40 1.10 0.89 0.26 0.26 0.10 HR (95% CI) --* --*
P (P-gp) 30 60 Lixiaa 30 warfari 3.05%) 4.85%) Lixiaa 60warfari( mitt )Lixiaa DVT PE DVT PE (VTE) Lixiaa Lixiaa Hokusai-VTE8,292(eoxapari ) Lixiaa 2.0 3.0warfariwarfari3 12( ) Lixiaa (69.6%)(21.0%) 3.8%5.3% 3Lixiaa 3,718 (91.6%)warfari 3,727 (91.4%) 6 Lixiaa 3,495 (86.1%)warfari 3,491 (85.6%)12 Lixiaa 1,643 (40.5%)warfari 1,659 (40.4%) 12 Lixiaa (CrCL 50/)P Hokusai-VTE( 10)()Lixiaa warfari Lixiaa 4,118130 (3.2%) warfari4,122146 (3.5%) p warfari 2.0 3.0) 65.6% ) 47 65 VTE) 10 Hokusai-VTE - mitt b a c ( ) / Lixiaa 60 (30 ) (N = 4,118) Warfari (N = 4,122) Lixiaa Warfari HR (95% CI) b p c 1.13) p ( ) warfari a DVT PEPE ) b CI Cox(PE DVTDVT) () Lixiaa Lixiaa 30 ( / ) P 1.5 30() Lixiaa warfari 15 (2.1%) 22 (3.1%) Lixiaa 138 (3.4%)warfari 158 (3.9%) VTE) [ Hokusai-VTELixiaa (30 )( ) 136 (3.3%)warfari130 (3.2%) Lixiaa warfari447 (30.6%) 483 (32.2%) / Lixiaa warfari14 (3.1%) 30 (6.2%) VTE) ( ) Hokusai-VTE () ( ) 11 ( )Lixiaa warfari Lixiaa 4,118349 (8.5%) warfari 4,122423 p
11 Hokusai-VTE - a ( b P Lixiaa 60 (30 ) (N = 4,118) ) 0 Warfari (N = 4,122) warfari a 3 b () Hokusai-VTEP (P-gp) 3058 92 0.86)] Hokusai-VTELixiaa warfari ( mitt )1.18) Lixiaa (4.2 ) 5.2 Lixiaa C max 62% C max Hokusai-VTE Lixiaa ph Lixiaa Lixiaa ( 4.5 ) 107±19.9 55% Lixiaa (1.14)3 Lixiaa Lixiaa ( 1) ( CYP3A4/5 Lixiaa 10%5% Lixiaa P- (P-gp)( / 50%/) 35%/ (t 1/2) 15 60Lixiaa Lixiaa Lixiaa /) (CrCL/) / ) 32% 74% 72% Lixiaa Lixiaa Xa 93% (CrCL 15-29/) CrCL Xa 12 CrCL Lixiaa Xa
12Lixiaa Xa Lixiaa 30 60 DVT PE DVT 30QD 2.21 60QD* 3.42 2.97 2.82 2.64 2.39 P- (P-gp)30 1 C max Lixiaa 1-3 ) 2 C mi CrCL (/) Lixiaa Lixiaa Xa(IU/mL) 1 Xa(IU/mL) 2 2.92 4.52 4.12 3.82 3.16 2.76 0.53 0.83 0.68 0.60 0.41 0.45 0.22 0.34 0.24 0.20 0.17 0.13 Lixiaa Lixiaa Xa( 4.4 ) 4 Lixiaa 9% Lixiaa ( 4.2 ) (84) (55) C max40% 13%( ) Lixiaa warfari Lixiaa 5.3 Lixiaa 200/( [/] 60/ 65 ) 300// ( 49 ) 200// ( 65 )600// ( 195 ) Lixiaa Lixiaa 6. 6.1 Crospovidoe Hydroxypropylcellulose Crospovidoe Hydroxypropylcellulose Crospovidoe Hydroxypropylcellulose
Talc Talc Hypromellose Talc 6.2 6.3 6.4 6.5 / 28 / 6.6 7. 2015 4 308 71