0916-DOR-01 5 / 5 /5 Dormicum Ampoules 5 mg/ml Midazolam Ampoules 5 mg/5ml 019457 019456 1. 1.1 / benzodiazepine ATC code: N05CD08. 1.2 1.3 1.4 / 1.5 midazolam( midazolam hydrochloride) Dormicum 5 /1 15 /3 5 /5 50 /10 Sodium chloride, hydrochloric acid, sodium hydroxide, water for injection. 1
2. 2.1 Dormicum () ( ) ( ) ( bolus ) 2.2 Midazolam 60 a) () Dormicum bolus ( ) 2 60 2.5 5-10 1 3.5-7.5 5.0 60 1.0 5-10 0.5-1 Dormicum 3.5 2
0.1-0.15 / 5-10 0.5 / 10.0 Dormicum Dormicum 2-3 2-3 5 6 6 6 6 5 0.05-0.1 / 0.6 / 6 6 12 0.025-0.05 / 0.4 / 10 12 16 b) Dormicum ( ) Dormicum Dormicum 20-60 ( )(good risk) (ASA I II 60 ) 0.07-0.1 /( 5 ) Dormicum 0.025-0.05 / 2-3 70 Dormicum 1-15 Dormicum 0.08-0.2 / Dormicum 30-60 Dormicum 0.4 / 0.3-0.5 / 20-30 3
10 () Dormicum Dormicum 25 % Dormicum 5 20-30 2 60 0.15-0.2 / 20-30 2 (good risk) (ASA I II) 0.2 / 60 (0.3-0.35 / 20-30 ) 2 25 % 0.6 / Dormicum 0.3 / Dormicum 0.2-0.25 / 0.15 / Dormicum ( 0.03-0.1 /) Dormicum ( 0.03-0.1 //) 60 ketamine (ataralgesia) Dormicum 0.15-0.20 / 2-3 c) 4
bolus Dormicum ( ) (loading dose) 1-2.5 20-30 2 0.03-0.3 / 15 (loading dose) Dormicum Dormicum 0.03-0.2 // 25% 2 3 0.05 0.2 / (Dormicum ) 0.06-0.12 //(1-2 / /) ( 25 %) Dormicum Dormicum Dormicum 32 0.03 //(0.5 //) 32 0.06 //(1 //) Dormicum (loading dose) 24 2.2.1 2.2 2.5 2.3 benzodiazepine 5
2.4 2.4.1 Midazolam Midazolam / 2.6 midazolam 60 - - - - 2.2 ) Dormicum Dormicum 6
2-3 Midazolam (anterograde amnesia) (Paradoxical reactions) (/) midazolam / Midazolam CYP3A4 midazolam midazolam 2.4.4 midazolam ( 2.5 ) 36 36 6 6 ( ) / Dormicum / Dormicum / 2.4.4 Dormicum (myasthenia gravis) midazolam 7
2.4.2 midazolam midazolam / 2.4.3 Dormicum 2.4.4 -(DDI) Midazolam P450 3A4 (CYP3A4) CYP3A midazolam CYP3A midazolam - ( valproic acid) ( ) Midazolam CYP3A midazolam midazolam CYP3A midazolam CYP3A midazolam CYP3A CYP3A ( [mechanism-based inhibition]) midazolam CYP3A ( clarithromycin erythromycin isoniazid) HIV ( HIV delavirdine) ( verapamil diltiazem)( gestodene raloxifene) ( ) ( ) ethinylestradiol/norgestrel (200 ) midazolam / ketoconazole CYP3A midazolam 5 rifampicin CYP3A rifampicin midazolam 60% 8
Midazolam CYP3A a) midazolam CYP3A midazolam b) CYP3A midazolam CYP3A midazolam CYP3A CYP3A c) midazolam CYP3A midazolam CYP3A midazolam - CYP3A midazolam midazolam midazolam - midazolam CYP3A Azole Ketoconazole midazolam 5 3 midazolam CYP3A ketoconazole(icu) / midazolam Fluconazole itraconazole midazolam 2-3 itraconazole fluconazole 2.4 1.5 Posaconazole midazolam 2 Erythromycin midazolam 1.6-2 midazolam 1.5-1.8 Clarithromycin midazolam 2.5 1.5-2 9
midazolam Roxithromycin Roxithromycin midazolam erythromycin clarithromycin midazolam 50% erythromycin clarithromycin midazolam 4.4 2.6 Roxithromycin midazolam 30% midazolam HIV Saquinavir HIV ritonavir lopinavir midazolam 5.4 midazolam HIV azole ketoconazole 2 Cimetidine midazolam 26% Diltiazem diltiazem midazolam 25% 43% midazolam Verapamil/diltiazem midazolam 3 4 Midazolam 41% 49% / Atorvastatin midazolam 1.4 midazolam Fluvoxamine midazolam (28%) Nefazodone midazolam 4.6 1.6 Aprepitant midazolam 80 / midazolam 3.3 2 Chlorzoxazone CYP3A α-hydroxymidazolam midazolam chlorzoxazone CYP3A Bicalutamide midazolam 27% 10
Goldenseal CYP3A α-hydroxymidazolam midazolam 40% goldenseal CYP3A CYP3A Rifampicin 7 rifampicin 600 midazolam 60% 50-60% midazolam Carbamazepine/phenytoin carbamezepine phenytoin midazolam 90% 60% Efavirenz CYP3A α-hydroxymidazolam midazolam 5 CYP3A (Echinacea purpurea root) midazolam 20% 42% (St John s wort) midazolam 20-40% 15-17% Valproic acidvalproic acid midazolam DDI valproic acid midazolam midazolam -(DDI) midazolam / () / /() benzodiazepine barbiturate propofol ketamine etomidate Midazolam (MAC) midazolam midazolam 2.4.1 < > 2.7 11
midazolam midazolam lidocaine bupivacaine midazolam /( AchE physostigmine) midazolam 250 midazolam 2.5 2.5.1 midazolam benzodiazepines midazolam benzodiazepines 2.5.2 Midazolam midazolam 24 2.5.3 2.2 2.4 15 1 / midazolam 1 / 6 ICU Dormicum 2.5.4 60 ( 2.2. 2.4 ) 12
2.5.5 midazolam α-hydroxymidazolam midazolam 1 midazolam () ( ) ± 37 27.8±37.2 0-140 24 13.6±16.4 0-58 9 44.6±42.5 2-120 2-124-140 2.5.6 midazolam midazolam 2.2 2.4 2.6 2.6.1 Dormicum paradoxical reactions(/ ) Dormicum 13
Dormicum 60 2.4 ) 60 2.4 (hiccup) benzodiazepine ( ) 2.7 Benzodiazepines Dormicum benzodiazepine Benzodiazepines () 1-2 / 14
CNS flumazenil ( ) benzodiazepine flumazenil ( 1 ) Flumazenil ( ) flumazenil ( ) 3. 3.1 3.1.1 Dormicum midazolam imidazobenzodiazepine imidazobenzodiazepine Dormicum Midazolam midazolam Dormicum ( 3.2 3.2.1 Midazolam 30 90% Midazolam 30 50% 3.2.2 Midazolam 0.7-1.2 / 96-98% Midazolam midazolam midazolam 15
3.2.3 Midazolam Midazolam cytochrome P450 3A4 α-hydroxymidazolam α-hydroxymidazolam 12% α-hydroxymidazolam midazolam ( 10%) midazolam 3.2.4 1.5-2.5 300-500 / Midazolam 60-80% glucuro αhydroxymidazolam 1% 1 midazolam bolus 3.2.5 60 2.4.1.) 2.5.4 5-18% 3-10 1-1.5 2.4.1.) 2.5.3 6-12 ( 2.4.1 )) ( 8.4 2.7 ) 50% ( 2.4.1 )) 16
2.4.1.) 2.5.3 2.5.5 midazolam ( 2.4.1 )) ( 2.4.1 )) 4. 4.1 (EXP) 4.2 Macrodex 6% Dextrose Dormicum Dormicum Midazolam sodium bicarbonate Dormicum 0.9%5% 10%5%(levulose) (Ringer's solution) Hartmann's 100-1000 15 midazolam 24 5 3 Dormicum 2-8 C 24 Dormicum 10 17
4.3 Ampoules 5 /5 019456 Ampoules 5 /1 15 /3 50 /10 019457 100 2014 10 CDS 6.0 10.14-DOR-3B02 3 134 9 02-2715-3111 Cenexi SAS. 52, Rue Marcel et Jacques Gaucher 94120 Fontenay-sous-Bois, France. ( ): 1 91 F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, CH-4070 Basel, Switzerland. Dormicum 18