0615-DOR-01 7.5 Dormicum Roche Film-Coated Tablets 7.5 mg Midazolam 017577 1. 1.1 / Dormicum benzodiazepines ATC code: N05CD08. 1.2 1.3 1.4 / 1.5 midazolam maleate midazolam 7.5 midazolam maleate anhydrous lactose microcrystalline cellulose pregelatinized starch magnesium stearate titanium dioxide talc hypromellose (Dormicum anhydrous lactose Lactose monohydrate 2.4.1 [ ]) 2. 2.1 (14 ) 2.2 1
2 Dormicum 7.5 15 Dormicum 30-60 2.2.1 / / 7.5 7.5 Dormicum 7-8 ( 3.2.5 ) midazolam 1 -hydroxymidazolam glucuronide 2.3 - - - - - benzodiazepines - - ketoconazole itraconazole voriconazole HIV ritonavir (boosted)( 2.4.5 ) 2
2.4 2.4.1 benzodiazepines benzodiazepines ( 2.2 ) 2 Dormicum ( ) Dormicum ( 2.4.2 ) Dormicum (anterograde amnesia) 7-8 ( 2.6 ) Dormicum 15 7-8 (Psychiatric and paradoxical reactions) benzodiazepines / 7.5 midazolam - Dormicum ( 2.2.1 ) 3
2.2.1 Benzodiazepines Benzodiazepines / Dormicum / Dormicum / ( 2.4. ) Dormicum. CYP3A Midazolam CYP3A ( 2.4. ) Lapp - 2.4.2 Dormicum / ( 2.2 2.4.1 [ ]) 4
2.4.3 ( 2.4.4 ) 2.4.4 -(DDI)( 2.3 2.4.1 [ ]) midazolam P450 3A (CYP3A) CYP3A midazolam CYP3A midazolam CYP3A midazolam CYP3A CYP3A ( [mechanism based inhibition]) midazolam CYP3A clarithromycin erythromycin HIV verapamil diltiazem ethinylestradiol/norgestrel()midazolam CYP3A CYP3A midazolam Midazolam 10 3 ketoconazole itraconazole voriconazole HIV ritonavir (boosted) midazolam CYP3A ( 2.3 ) Midazolam 5 10 3 Midazolam 2 5 2 3 fluconazole clarithromycin telithromycin erythromycin diltiazem verapamil nefazodone aprepitant tabimoreline midazolam CYP3A midazolam ( 2.4.1 [ 5
]) Midazolam 1.25 2 1.25 2 posaconazole roxithromycin cimetidine ranitidine fluvoxamine bicalutamide propiverine grapefruit juice echinacea purpurea goldenseal midazolam CYP3A midazolam CYP3A midazolam CYP3A midazolam CYP3A CYP3A rifampicin carbamazepine phenytoin efavirenz St John s wort -(DDI) midazolam // /() benzodiazepines (barbiturates)propofol ketamine etomidate Midazolam (MAC) midazolam () midazolam ( 2.4.1 ( )) () 2.7 /( AchE physostigmine) midazolam 250 midazolam 2.5 2.5.1 midazolam benzodiazepines 6
midazolam benzodiazepines benzodiazepines 2.5.2 2.5.1 2.5.3 midazolam Dormicum 2.5.4 2.3 2.5.5 2.2.1 2.4.1 ( ) 2.5.6 2.2.1 2.6 2.6.1 : : benzodiazepines (Psychiatric and paradoxical reactions) benzodiazepines benzodiazepines 7
( ) ( 2.4.1 [ ]) : ( 2.4.1 [ ]) : : : : : benzodiazepine ( ) : : 2.7 Benzodiazepines Dormicum benzodiazepine Benzodiazepines () 8
1-2 / flumazenil ( ) benzodiazepine flumazenil ( 1 ) Flumazenil ( ) flumazenil ( ) 3. 3.1 3.1.1 Dormicum /Dormicum benzodiazepines Dormicum gamma-aminobutyric acid(gaba A ) benzodiazepines GABA A GABA 3.2 3.2.1 Midazolam midazolam 30-70% 7.5-20 midazolam Dormicum 15 1 70-120ng/ midazolam 5-20 3.2.2 midazolam 1-2 0.7-1.2 / 9
96-98% Midazolam midazolam midazolam 3.2.3 Midazolam 1% Midazolam cytochrome P450 CYP3A CYP3A4 CYP3A5 midazolam 1 -hydroxymidazolam ( α-hydroxymidazolam) 4-hydroxymidazolam 1 -hydroxymidazolam 60-80% glucuronic acid 1 -hydroxymidazolam conjugate 1 -hydroxymidazolam 30-50% 1 -hydroxymidazolam midazolam ( 34%) midazolam 3.2.4 midazolam 1.5-2.5 midazolam midazolam 1 -hydroxymidazolam 1 3.2.5 60 midazolam 2.5 midazolam midazolam midazolam midazolam midazolam 1 -hydroxymidazolam glucuronide 10
midazolam midazolam midazolam (5.9 2.3 ) midazolam 4. 4.1 5. 2-1000 017577 2014 10 CDS 4.0 10.14-DOR-3B01 3 134 9 02-2715-3111 F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, CH-4070 Basel, Switzerland. Productos Roche, S.A. de C.V.. Via Isidro Fabela Nte. No.1536-B, CP 50030, Toluca, Mexico. F. Hoffmann-La Roche Ltd. Wurmisweg, CH-4303 Kaiseraugst, Switzerland. Dormicum 11